Original Article
Effect of Intermittent Cyclical Etidronate Therapy on Bone Mass and Fracture Rate in Women with Postmenopausal Osteoporosis
N Engl J Med 1990; 322:1265-1271May 3, 1990
- Abstract
- Abstract
Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity.
The patients were randomly assigned in equal numbers to receive oral etidronate (400 mg per day) or placebo for 2 weeks, followed by a 13-week period in which no drugs were given. This sequence was repeated 10 times, for a total of 150 weeks. Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups. Vertebral bone mineral content was measured by dual-photon absorptiometry; spinal radiographs were assessed to identify new vertebral fractures.
Vertebral bone mineral content increased significantly (P<0.01) after 150 weeks of etidronate therapy (5.3 percent; 95 percent confidence interval, 2.0 to 8.6; n = 20) but decreased with placebo (–2.7 percent; 95 percent confidence interval, –7.3 to 1.9; n = 20). The difference between groups was 8.0 percentage points (P<0.01; 95 percent confidence interval, 2.4 to 13.6). The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups (6 vs. 54 fractures per 100 patient-years; P = 0.023). No adverse clinical, biochemical, or bone histomorphometric effects of treatment were observed.
We conclude that at the end of nearly three years, etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and, after approximately one year of treatment, a significant decrease in the rate of new vertebral fractures. (N Engl J Med 1990; 322:1265–71.)
Media in This Article
Figure 1
Change in the Bone Mineral Content of the Lumbar Vertebrae (L-2 to L-4) in Postmenopausal Patients with Osteoporosis Who Received Intermittent Cyclical Therapy with Etidronate (Solid Circles) or Placebo (Open Circles).Figure 2
Annual Rates of Change in the Bone Mineral Content of the Lumbar Vertebrae (L-2 to L-4) in Postmenopausal Patients with Osteoporosis Who Completed 150 Weeks of Intermittent Cyclical Therapy.Article Activity
- Article
POSTMENOPAUSAL osteoporosis is characterized by an absolute decrease in the amount of bone, leading to fractures after minimal trauma, most frequently of the vertebrae, the proximal femur, and the distal forearm. Since the progression of bone loss is due to an imbalance between bone resorption and bone formation, with the former exceeding the latter, drugs that can inhibit resorption are attractive candidates for the treatment of osteoporosis.
Etidronate disodium (etidronate) is an oral diphosphonate compound known to reduce bone resorption through the inhibition of osteoclastic activity.1 It has been used for the treatment of Paget's disease of bone for more than a decade and has been shown to have minimal toxicity.2 , 3 In 1976, Heaney and Saville4 demonstrated that continuous treatment of osteoporosis with etidronate at a dose of 20 mg per kilogram of body weight per day for 6 to 12 months resulted in a 50 percent reduction in bone resorption and a slight but significant increase in calcium balance. However, these investigators observed a depression in bone mineralization of a similar magnitude and suggested that treatment at 5 to 10 mg per kilogram per day might produce a better separation between the effects of etidronate on bone resorption and mineralization. In 1984, Anderson and his colleagues5 reported preliminary observations on a form of "coherence therapy" for osteoporosis. The underlying concept of coherence therapy6 is that the sequential stimulation and depression of osteoclastic activity will induce a synchronization of bone resorption and formation. After the activation of osteoclasts with a pharmacologic agent such as phosphorus or parathyroid hormone, a second agent, such as etidronate, is administered for a limited time to depress osteoclastic activity. Treatment is then stopped for a time to allow for normal osteoblastic function. This cycle is repeated, and theoretically, each treatment cycle would effect a gain in bone mass. The treatment regimen used by Anderson and colleagues involved the administration of phosphorus for 3 days, followed by etidronate (5 mg per kilogram per day) for 15 days and then a medication-free period of 10 weeks; the cycle was repeated for 9 to 24 months. This intermittent cyclical treatment resulted in marked improvements in bone mass, as evaluated by bone histomorphometry.
We tested a regimen for the treatment of postmenopausal osteoporosis consisting of the intermittent cyclical administration of oral etidronate without the preactivation of osteoclasts. We report the results of a three-year, randomized, double-blind, placebo-controlled study of the effects of this treatment regimen on bone mass, the progression of vertebral deformity, the loss of height, and the rate of fracture in a group of postmenopausal women with osteoporosis.
Methods
Patients
Sixty-six postmenopausal women with osteoporosis (mean age, 68.3 years; range, 56 to 75) were enrolled in the randomized, double-blind, placebo-controlled study between October 1983 and April 1986. The study was approved by the Copenhagen and Frederiksberg ethics committee for implementation at Sundby Hospital in Copenhagen, and informed, written consent was obtained from all participants.
Inclusion in this study was based on evidence of osteoporosis, as determined by the presence of at least one but not more than four atraumatic vertebral crush fractures and radiographically confirmed demineralization of vertebrae. Patients were excluded if they had secondary causes of osteoporosis, such as hyperparathyroidism, Paget's disease of bone, or renal osteodystrophy; impairment of renal, cardiac, or thyroid function; or a history of therapy with corticosteroids, estrogens, calcitonin, calcium, or vitamin D for three months or longer during the six months preceding study entry, or any such treatment during the two months preceding study entry. Patients were also excluded if they had received fluoride or diphosphonate therapy for any disease.
The patients were assigned to one of two study groups by means of computer-generated random numbers. Patients received 400 mg (5 to 10 mg per kilogram per day) of oral etidronate (Didronel, Norwich Eaton Pharmaceuticals, Norwich, N.Y.) or placebo daily for 2 weeks, followed by a 13-week period in which no drugs were given. Daily calcium consumption from dietary sources was not recorded, and no dietary restrictions or changes were implemented during the study. To ensure adequate calcium intake, all patients received daily supplements of elemental calcium (500 mg in the form of an effervescent tablet composed of calcium lactate gluconate and calcium carbonate; Calcium-Sandoz, Sandoz Pharmaceuticals, Basel, Switzerland) and a multivitamin containing 400 IU of vitamin D throughout the 15-week study cycle. The calcium and vitamin D supplements were taken in the morning, and patients were instructed to take the study drug (i.e., etidronate or placebo) with water in the afternoon at the midpoint of a four-hour fast. All patients were to receive 10 cycles of treatment lasting 15 weeks; the total study period thus lasted 150 weeks.
Measurement of Regional Bone Mineral Content
Bone mineral content was measured at two clinically important sites with different compositions of trabecular and cortical bone, at base line and every 30 weeks thereafter. All measurements and calculations were performed by an observer who was unaware of the treatment assignment.
The bone mineral content of the lumbar spine was measured by dual-photon absorptiometry with gadolinium-153 (BMC-LAB 22a, Novo Diagnostic Systems, Bagsvaerd, Denmark) and was calculated as the sum of the scan integrals over the second, third, and fourth lumbar vertebrae and expressed as the total bone mineral content in grams of hydroxyapatite.7 Since the total bone mineral content (and not the density of bone mineral) was calculated, we did not exclude values for vertebrae with compression fractures. To ensure that similar regions were analyzed at each interval, all calculations for a patient were done with reference to a previous measurement. If a new fracture had occurred in the region of interest, the number of scan integrals was adjusted accordingly. The coefficient of variation in healthy young subjects is 2 to 3 percent, and in patients with osteoporosis 4 to 5 percent.
The regional bone mineral content of the distal nondominant forearm was measured by single-photon absorptiometry with iodine-125 (Novo GT 35, Novo Diagnostic Systems).8 The bone mineral content was calculated as the sum of the scan integrals of six scans and expressed in arbitrary units; 1 arbitrary unit corresponds to approximately 0.07 g of hydroxyapatite. The measurement site was the point at which the distance between the radius and the ulna exceeded 8 mm; the five subsequent scans were performed proximal to this site at intervals of 4 mm. Scan integrals included both the radius and ulna. The coefficient of variation in healthy young subjects is 1 to 2 percent, and in patients with osteoporosis 3 to 4 percent.
Determination of Spinal-Deformity Index and Fracture Rate
Radiographs of the thoracic (T-4 to T-12) and lumbar (L-1 to L-4) spine obtained at base line and weeks 60, 120, and 150 were evaluated by an independent radiologist who was unaware of the patient's assigned group. For each patient, a semiquantitative vertebral-deformity score9 , 10 was assigned to individual vertebrae according to the following criteria: a normal, unfractured vertebra was assigned a grade of zero; a mild fracture with a 20 to 25 percent reduction in anterior, middle, or posterior height (or all three) accompanied by a reduction in area of approximately 10 to 20 percent was assigned a grade of 1; a moderate fracture with a 25 to 40 percent reduction in any height accompanied by a reduction in area of approximately 20 to 40 percent was assigned a grade of 2; and a severe fracture with a reduction of more than 40 percent in any height and accompanying area was assigned a grade of 3. Intermediate grades (increments of 0.5) were also used as appropriate. The vertebrae were generally not measured directly; however, a patient's entire series of films was viewed simultaneously in chronologic sequence to accommodate the potential overlap in grading criteria. In scoring each vertebra, consideration was given to the configuration of the vertebral end plates (i.e., biconcavity and sharp, angular deformities) and the size and shape of the adjacent vertebrae; only definite and substantial changes in these characteristics constituted a basis for assigning a higher score on the serial films.
A spinal-deformity index (the sum of the individual vertebral-deformity scores divided by the number of vertebrae evaluated) was calculated for each patient at each evaluation (base line and weeks 60, 120, and 150); changes in the mean indexes of each group for each study interval were also calculated from the values for individual patients. In addition, the rate of new vertebral fractures per 100 patient-years was calculated for each group. Only new vertebral fractures were identified; a new fracture was deemed to have occurred if a vertebra with an earlier grade of zero was assigned a grade of 1 or higher at a subsequent study visit. Clinically overt nonvertebral fractures and the time of their occurrence during the study were also recorded.
Height
The patient's height was measured at base line and every 30 weeks thereafter in the morning.
Serum and Urine Measurements
Fasting serum chemistry profiles for ionized calcium, phosphorus, and alkaline phosphatase and urine chemistry profiles for the 24-hour excretion of hydroxyproline and creatinine were obtained at base line and every 15 weeks thereafter. Patients were not restricted to a hydroxyproline-free diet before the urine was collected.
The serum ionized calcium concentration was determined with an ion-selective electrode (ICA 1, Radiometer, Copenhagen, Denmark). Serum phosphorus and serum alkaline phosphatase levels were determined by spectrophotometry (Cobas-Mira, Roche, Basel, Switzerland). Urinary creatinine concentration was analyzed by Jaffé chromogen reaction (Astra, Beckman Instruments, Palo Alto, Calif). Urinary hydroxyproline concentration was analyzed as described by Kivirikko et al.11 by means of spectrophotometry (PU 8600, Pye Unicam, Cambridge, United Kingdom).
Bone Histomorphometric Evaluation
Biopsy samples of the transiliac crest were obtained at base line and weeks 60 and 150 for histomorphometric evaluation. The biopsy samples were removed from the standard region 2 cm below and 2 cm behind the anterior superior iliac spine12 after intravital double labeling with tetracycline (administered 14, 13, 4, and 3 days before biopsy).13 The histomorphometric analyses and the applied stereologic transformations have been described previously in detail.14 15 16 The evaluation was done by an observer who was unaware of the treatment assignment. Changes in the volume of trabecular bone, the rate of bone turnover, and selected measurements (the osteoid surface, osteoid thickness, and mineralization lag time) performed for reasons of safety are presented here.
Evaluation of Side Effects
All clinical side effects and deaths that occurred during the study were recorded, and their causes were evaluated.
Statistical Analysis
Two-tailed t-tests (P = 0.05) were used to compare group data at base line. Because a level of significance of 0.025 was used for interim analyses,17 the level was adjusted to 0.034 in the final analyses of the results to preserve an overall P value of 0.05.18 All tests were two-tailed, and the data are shown as means ±SEM. Ninety-five percent confidence intervals were calculated for the values of bone mineral content of the vertebrae and distal forearm.
Comparisons of base-line values with serial measurements determined by dualphoton and single-photon absorptiometry (weeks 90, 120, and 150) were performed within groups by one-sample t-tests, and between groups by two-sample t-tests. For each patient who completed 150 weeks of treatment, linear regression analysis (zero-intercept model) was performed on the percent changes in vertebral bone mineral content from base line as a function of the number of weeks of study. The mean slopes from the regression equations were then used to calculate the mean rate of change in bone mineral content per year for each group. The mean rates of change for the two groups were compared with a two-sample t-test.
Comparisons between groups in the changes in the spinal-deformity index were performed at each study interval by means of the Wilcoxon rank-sum test. The fracture rate per 100 patient-years was calculated for each patient on the basis of the number of new vertebral fractures occurring in the periods from base line to week 150, base line to week 60, and week 60 to week 150. The Wilcoxon rank-sum test was used to compare the fracture rate in the groups. Although these data were analyzed by nonparametric methods, the mean fracture rate per 100 patient-years is provided for comparison with the results of other studies.
Comparisons of changes within groups and between groups in height, serum levels of alkaline phosphatase, and the ratio of urinary hydroxyproline to urinary creatinine were evaluated with one-sample and two-sample t-tests as appropriate. Changes in bone histomorphometric values were evaluated with the Wilcoxon rank-sum test.
Results
The demographic and base-line clinical features of the study patients are presented in Table 1Table 1
Demographic and Base-Line Clinical Characteristics of Postmenopausal Patients with Osteoporosis at Study Entry.*. At entry, the groups were comparable in age, time since menopause, height, weight, bone mineral content of the vertebrae and distal forearm, spinal-deformity index, and biochemical markers of bone turnover. Of the 66 patients initially enrolled, 13 in the etidronate group and 13 in the placebo group left the study because of noncompliance with the study regimen (1 and 0, respectively), intercurrent illness (2 and 2), voluntary withdrawal (5 and 6), or death (5 and 5).Bone Mineral Content
Figure 1Figure 1
Change in the Bone Mineral Content of the Lumbar Vertebrae (L-2 to L-4) in Postmenopausal Patients with Osteoporosis Who Received Intermittent Cyclical Therapy with Etidronate (Solid Circles) or Placebo (Open Circles). shows the changes in the mean bone mineral content of vertebrae during the study period. A significant increase (P<0.01) from base line to week 150 was seen in the etidronate group (5.3 percent; 95 percent confidence interval, 2.0 to 8.6); the decrease in bone mineral content from base line to week 150 in the placebo group (−2.7 percent; 95 percent confidence interval, −7.3 to 1.9) was not statistically significant. The difference between the groups was 8.0 percent (P<0.01; 95 percent confidence interval, 2.4 to 13.6).Regression analysis of the percent change in vertebral bone mineral content from base line as a function of the number of weeks of study for the patients who completed 150 weeks of the study showed a significant difference (P = 0.001) between the mean rates of change in the etidronate (n = 20) and placebo (n = 20) groups (2.2 and −1.4 percent per year, respectively; 95 percent confidence intervals, 1.0 to 3.4 and −3.0 to 0.2, respectively) (Fig. 2Figure 2
Annual Rates of Change in the Bone Mineral Content of the Lumbar Vertebrae (L-2 to L-4) in Postmenopausal Patients with Osteoporosis Who Completed 150 Weeks of Intermittent Cyclical Therapy.). According to an arbitrary criterion for response to treatment (i.e., a positive slope of the regression equation), the rate of response in the etidronate group was 85 percent (17 of 20 patients) and 30 percent (6 of 20 patients) in the placebo group.At week 150, the mean percent change in the bone mineral content of the distal forearm was not significantly different from zero in either the etidronate group (1.5 percent; 95 percent confidence interval, − 3.5 to 6.5; n = 20) or the placebo group (−3.6 percent; 95 percent confidence interval, −7.4 to 0.2; n = 20) (Fig. 3Figure 3
Change in the Bone Mineral Content of the Nondominant Distal Forearm in Postmenopausal Patients with Osteoporosis Who Received Intermittent Cyclical Therapy with Etidronate (Solid Circles) or Placebo (Open Circles).). The difference between the groups was 5.1 percent (95 percent confidence interval, −1.1 to 11.3).Spinal-Deformity Index and Fracture Rate
During the first 60 weeks of treatment, a similar rate of deterioration in vertebral integrity, as represented by increasing mean spinal-deformity indexes, was observed in the two groups; thereafter, however, the mean index remained relatively constant in the etidronate group but rose progressively in the placebo group. The difference between the groups in terms of the change in the spinal-deformity index from base line was significant at week 150 (P = 0.028) (Fig. 4Figure 4
Change in the Spinal-Deformity Index in Postmenopausal Patients with Osteoporosis Who Received Intermittent Cyclical Therapy with Etidronate (Solid Circles) or Placebo (Open Circles).).No significant difference between the etidronate and placebo groups was observed in the rate of new vertebral fractures for the period from base line to week 150 (18 and 43 per 100 patient-years, respectively) or from base line to week 60 (38 and 35 per 100 patient-years, respectively); however, the rates for the period from week 60 to week 150 were significantly different (6 and 54 per 100 patient-years, respectively; P = 0.023).
Spontaneous and traumatic nonvertebral fractures occurred in both groups during the study. Six patients receiving placebo had a total of 10 nonvertebral fractures (forearm, 3; hip, 2; humerus, 2; pelvis, 1; maxillary, 1; and sternum, 1), and five patients receiving etidronate had a total of 6 nonvertebral fractures (forearm, 2; femur, 1; hip, 1; rib, 1; and finger, 1). Among the patients who received placebo, seven nonvertebral fractures were reported during or before week 60 of the study, two during week 90, and one during week 135. All nonvertebral fractures in the patients who received etidronate occurred before week 60.
Height
The mean changes in height in both groups were significantly different from zero (P<0.01); however, there was less loss of height in the etidronate group than in the placebo group (−1.1 ±0.3 vs. −1.9±0.4 cm) (Fig. 5Figure 5
Change in Height in Postmenopausal Patients with Osteoporosis Who Received Intermittent Cyclical Therapy with Etidronate (Solid Circles) or Placebo (Open Circles).). The difference between the two groups was not statistically significant (P = 0.15).Biochemical Analyses
The mean serum levels of calcium were unchanged in both groups over the 150-week study period. Serum phosphorus levels in the placebo group were stable during the study period, whereas levels in the etidronate group showed minimal increases at the end of the two-week administration period during each treatment cycle (data not shown); such increases are consistent with the known pharmacologic action of this diphosphonate in increasing the tubular reabsorption of phosphate by the kidney.2 Significant decreases (P<0.01) in the serum levels of alkaline phosphatase were observed in the etidronate group at weeks 30, 60, 120, and 150, whereas no significant changes occurred in the placebo group during the study. The difference between the groups in the mean levels of this biochemical marker of bone turnover was significant (P<0.02) at week 150. No changes in the ratio of urinary hydroxyproline to urinary creatinine were noted in either group at any time; these results were most likely due to the 24-hour urine collections and to the absence of dietary restrictions before urine collection.
Bone Histomorphometric Evaluation
Biopsy samples of bone were obtained from all patients in the study. However, usable biopsy samples were obtained at both week 0 and week 60 only in 20 patients treated with etidronate and 21 given placebo; usable samples were obtained at both week 0 and week 150 in 14 patients treated with etidronate and 15 given placebo. No change from base line in the mean volume of trabecular bone was found at either time in the two groups. Etidronate treatment did not result in an accumulation of unmineralized bone, as evidenced by the lack of change in osteoid surface and thickness. The mineralization lag time (i.e., the average lag time between the formation and subsequent mineralization of osteoid) also remained unchanged. Thus, no signs of osteomalacia could be detected after either 60 or 150 weeks of etidronate treatment.
After 60 weeks of etidronate treatment, a significant decrease (−58 percent; P<0.02) in the rate of bone turnover was observed. After 150 weeks of treatment, the rate of bone turnover appeared to return toward base line (−11 percent as compared with base line values; P>0.05). In the placebo group, no change in the rate of bone turnover was seen at week 60, but a significant increase was observed after 150 weeks (79 percent; P<0.02).
Side Effects
Oral etidronate was well tolerated; no significant side effects related to the study drug were observed. Serial serum and urine assays revealed no significant, unexplained, or unanticipated abnormalities. Ten deaths (5 in each treatment group) occurred during the study but were not related to the study drugs or to the patients' osteoporosis.
Discussion
The results of our study demonstrate that intermittent cyclical therapy with oral etidronate is effective in reversing the progressive loss of vertebral bone that occurs in postmenopausal osteoporosis. By measuring bone mass at two clinically relevant sites, the vertebrae and distal forearm, we were able to evaluate the effects in areas with predominantly trabecular and cortical bone, respectively. In the patients who received etidronate, the significant increases in vertebral bone mineral content were accompanied by small but not statistically significant increases in the bone mineral content of the forearm, suggesting that the increases in trabecular bone mass were not attained at the expense of cortical bone mass.
The course of the response in the etidronate group over time, as assessed by changes in vertebral bone mineral content, is in accordance with that reported by other trials in which antiresorptive agents have been administered: an early increase in bone mass was followed by a plateau.19 20 21 22 23 Two different mechanisms may be involved. Parfitt24 postulated that the increase in bone mineral content may be due to a decrease in bone remodeling as the resorption cavities are filled in. Once the empty resorption cavities are filled, no further increment in bone mass occurs, and the plateau effect is observed. Furthermore, a decrease in the rate of bone turnover naturally leads to an increase in the mean age of the bone, and since older bone is more heavily mineralized, the bone mineral content may increase. Since continuous oral treatment with high doses of etidronate may lead to the impairment of bone mineralization and the cessation of bone remodeling,4 , 25 a more ideal therapeutic regimen might consist of the intermittent cyclical administration of the diphosphonate in a dose that inhibits bone resorption yet does not prevent mineralization. Although we do not know whether the dose and treatment regimen used in our study are optimal, our results are encouraging. We could detect no signs of osteomalacia after either 60 or 150 weeks of treatment with etidronate.
Several other studies have been completed5 , 23 , 26 , 27 or are under way22 in which etidronate is administered cyclically and intermittently as part of a regimen of coherence therapy. Reports of increases in bone mass in studies in which coherence therapy with phosphorus and etidronate has been used22 , 23 are consistent with the results of our study, suggesting that the use of phosphorus in the treatment regimen may not be essential for the effect. Unlike other potential inhibitors of bone resorption, such as calcitonin, etidronate may have a prolonged action on bone despite intermittent administration. Because diphosphonates are adsorbed onto bone and are resistant to hydrolysis, the activation of osteoclasts with phosphorus may theoretically be counteracted when etidronate first is adsorbed onto bone. Thus, the results of coherence-therapy studies that used diphosphonates as the antiresorbing agents could be due to the effects of the diphosphonates alone.
Pacifici and coworkers reported that intermittent treatment with phosphorus and etidronate did not prevent the loss of vertebral bone.26 Because they administered etidronate and calcium twice daily (and even though patients were instructed not to take the etidronate with meals or with the calcium tablets), it is possible that the absence of efficacy was due to diminished absorption of etidronate. Only 1 to 9 percent of a single dose of etidronate is absorbed, and absorption is further diminished by the presence of calcium and dairy products.3 , 28 Therefore, it seems of major importance that etidronate be taken with water at the midpoint of a four-hour fast.
Intermittent cyclical therapy with etidronate induced an increase in the bone mineral content of vertebrae, followed by a reduction in the rate of deterioration of vertebral integrity (as measured by the spinal-deformity index) and the rate of vertebral fracture. Compression fractures of the vertebral bodies are the result of a weakening of the trabecular structure due to the thinning or perforation of already compromised trabecular plates and rods.29 In patients who already have some fractured vertebrae, it must be assumed that the remaining intact vertebrae are also perilously close to fracture. We were unable to demonstrate an increase in the volume of trabecular bone, as assessed by bone histomorphometry, and it can therefore be inferred that intermittent cyclical treatment with etidronate maintains the mechanical competence of critical structural elements in bone or otherwise prevents their further compromise. In our study, histomorphometric analyses of bone showed a significant decrease in the rate of bone turnover after 60 weeks of etidronate therapy. The apparent return toward base line after 150 weeks probably represents a regional acceleration of turnover, since both the first biopsy samples (week 0) and the third biopsy samples (week 150) were obtained from the right iliac crest and an increase in the rate of turnover was noted in the placebo group after 150 weeks. We suggest that the overall reduction in the rate of bone turnover in the etidronate group was followed by a reduction in the rate of new perforations of bone structural elements and thus helped prevent further vertebral deformities and fractures. Furthermore, because of the long remodeling cycle in osteoporosis, the effects of antiresorptive agents such as etidronate are not likely to be fully appreciated during the first year of treatment. This is consistent with the results of our study. The degree of protection afforded appears to depend on the duration of therapy, since it is much higher during the second and third years of treatment and results in the prevention of new vertebral fractures.
In summary, intermittent cyclical therapy with oral etidronate results in small but significant increases in the bone mineral content of vertebrae and, after approximately one year of treatment, a stabilization in the progression of spinal deformity and a significant decrease in the rate of new vertebral fractures.
Supported by a research grant from Norwich Eaton Pharmaceuticals, a Procter & Gamble company.
We are indebted to Ms. Eva Hermann, Ms. Birgit Ludvigsen, and Ms. Ulla Pedersen for their skillful technical assistance and to the Departments of Radiology and Clinical Chemistry at Sundby Hospital.
Source Information
From the Department of Medicine, Sundby Hospital, Copenhagen, Denmark (T. Storm, G.T., O.H.S.); the University Institute of Pathology, Aarhus Amtssygehus, Aarhus, Denmark (T. Steiniche); and the Departments of Radiology, Medicine, and Orthopedic Surgery, University of California, San Francisco (H.K.G.). Address reprint requests to Dr. Storm at the Department of Medicine, Sundby Hospital, 2300 Copenhagen S, Denmark.
- References
References
1
Guncaga
CrossRef | Web of Science | Medline2
Fleisch
CrossRef | Medline3
Fleisch
Web of Science | Medline4
Heaney
Web of Science | Medline5
Anderson
CrossRef | Web of Science | Medline6
Frost
Web of Science | Medline7
Krølner
CrossRef | Web of Science | Medline8
Christiansen
CrossRef | Web of Science | Medline9
Ettinger
CrossRef | Web of Science | Medline10
Richardson
Web of Science | Medline11
Kivirikko
CrossRef | Web of Science | Medline12
Bordier
Web of Science | Medline13
Frost
CrossRef | Medline14
Meisen
Medline15
Eriksen
CrossRef | Medline16
Eriksen
CrossRef | Medline17
Storm T, Thamsborg G, Sørensen OH, Lund B. The effects of etidronate therapy in postmenopausal osteoporotic women: preliminary results. In: Christiansen C, Johansen JS, Riis BJ, eds. Osteoporosis 1987: International Symposium on Osteoporosis, Denmark, 1987, Sept. 27-Oct. 2. Vol. 2. Copenhagen: Osteopress ApS, 1987:1172–6.
18
Pocock
CrossRef | Web of Science | Medline19
Gruber
CrossRef | Web of Science | Medline20
Gennari
Web of Science21
Mazzuoli
CrossRef | Web of Science | Medline22
Genant HK, Harris ST, Steiger P, Davey PF, Block JE. The effect of etidronate therapy in postmenopausal osteoporotic women: preliminary results. In: Christiansen C, Johansen JS, Riis BJ, eds. Osteoporosis 1987: International Symposium on Osteoporosis, Denmark, 1987, Sept. 27-Oct. 2. Vol. 2. Copenhagen: Osteopress ApS, 1987:1177–81.
23
Hodsman
CrossRef | Medline24
Parfitt 25
Kanis
Web of Science | Medline26
Pacifici
CrossRef | Web of Science | Medline27
Hesch
CrossRef | Medline28
Fogelman
CrossRef | Web of Science | Medline29
Kanis
CrossRef | Web of Science | Medline
- Citing Articles (294)
Citing Articles
1
Richard Eastell, Jennifer S. Walsh, Nelson B. Watts, Ethel Siris. (2011) Bisphosphonates for postmenopausal osteoporosis. Bone 49:1, 82-88
CrossRef2
Glen M. Blake, Michelle L. Frost, Amelia E.B. Moore, Musib Siddique, Ignac Fogelman. (2011) The Assessment of Regional Skeletal Metabolism: Studies of Osteoporosis Treatments Using Quantitative Radionuclide Imaging. Journal of Clinical Densitometry 14:3, 263-271
CrossRef3
R. Graham G. Russell. (2011) Bisphosphonates: The first 40years. Bone 49:1, 2-19
CrossRef4
Michelle L Frost, Musib Siddique, Glen M Blake, Amelia EB Moore, Paul J Schleyer, Joel T Dunn, Edward J Somer, Paul K Marsden, Richard Eastell, Ignac Fogelman. (2011) Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography. Journal of Bone and Mineral Research 26:5, 1002-1011
CrossRef5
José Manuel Quesada Gómez, Josep Blanch Rubió, Manuel Díaz Curiel, Adolfo Díez Pérez. (2011) Calcium Citrate and Vitamin D in the Treatment of Osteoporosis. Clinical Drug Investigation1
CrossRef6
Robert B Hopkins, Ron Goeree, Eleanor Pullenayegum, Jonathan D Adachi, Alexandra Papaioannou, Feng Xie, Lehana Thabane. (2011) The relative efficacy of nine osteoporosis medications for reducing the rate of fractures in post-menopausal women. BMC Musculoskeletal Disorders 12:1, 209
CrossRef7
Nathan B. Helm, Soumya Padala, F. Michael Beck, Andrew M. D’Atri, Sarandeep S. Huja. (2010) Short-term zoledronic acid reduces trabecular bone remodeling in dogs. European Journal of Oral Sciences 118:5, 460-465
CrossRef8
Thomas Marc Link. (2010) The Founder’s Lecture 2009: advances in imaging of osteoporosis and osteoarthritis. Skeletal Radiology 39:10, 943-955
CrossRef9
Bassant A. Ezzat. (2010) Validity of prevention of glucocorticoid-induced alveolar bone loss in rat by either calcitonin or alendronate administration. Archives of Oral Biology 55:10, 788-796
CrossRef10
Jeong-Hyun Jee, Wan Lee, Byung Do Lee. (2010) The influence of alendronate on the healing of extraction sockets of ovariectomized rats assessed by in vivo micro–computed tomography. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 110:2, e47-e53
CrossRef11
Bo Abrahamsen. (2010) Adverse Effects of Bisphosphonates. Calcified Tissue International 86:6, 421-435
CrossRef12
Yoshihiro Sato, Jun Iwamoto, Yoshiaki Honda. (2010) Beneficial Effect of Etidronate Therapy in Chronically Hospitalized, Disabled Patients with Stroke. Journal of Stroke and Cerebrovascular Diseases 19:3, 198-203
CrossRef13
Glen M. Blake, Ignac Fogelman. (2010) An Update on Dual-Energy X-Ray Absorptiometry. Seminars in Nuclear Medicine 40:1, 62-73
CrossRef14
Glen M. Blake, Ignac Fogelman. (2009) The clinical role of dual energy X-ray absorptiometry. European Journal of Radiology 71:3, 406-414
CrossRef15
B. Abrahamsen, P. Eiken, K. Brixen. (2009) Atrial fibrillation in fracture patients treated with oral bisphosphonates. Journal of Internal Medicine 265:5, 581-592
CrossRef16
, Hans Peter Dimai, Peter Pietschmann, Heinrich Resch, Elisabeth Preisinger, Astrid Fahrleitner-Pammer, Harald Dobnig, Klaus Klaushofer. (2009) Österreichischer Leitfaden zur medikamentösen Therapie der postmenopausalen Osteoporose – Update 2009. Wiener Medizinische Wochenschrift 159:S122, 1-34
CrossRef17
M. Sosa Henríquez, M.J. Gómez de Tejada Romero. (2009) La medicina basada en la evidencia y los fármacos aprobados para el tratamiento de la osteoporosis. Papel del calcio y la vitamina D. Revista Clínica Española 209:1, 25-36
CrossRef18
Jin Young Kim, Eun Su Moon, Hwan Mo Lee, Seong Hwan Moon, Jin Oh Park, Jee Ho Hyung, Hak Sun Kim. (2009) Prevention of New Vertebral Fractures after Treatment with Risedronate, Alendronate or Calcium Carbonate in Patients with Osteoporotic Compression Fracture Treated with Cement Augmentation. The Journal of the Korean Orthopaedic Association 44:4, 436
CrossRef19
Brian L. Foster, Kevin A. Tompkins, R. Bruce Rutherford, Hai Zhang, Emily Y. Chu, Hanson Fong, Martha J. Somerman. (2008) Phosphate: Known and potential roles during development and regeneration of teeth and supporting structures. Birth Defects Research Part C: Embryo Today: Reviews 84:4, 281-314
CrossRef20
J Sarin, SS DeRossi, SO Akintoye. (2008) Updates on bisphosphonates and potential pathobiology of bisphosphonate-induced jaw osteonecrosis. Oral Diseases 14:3, 277-285
CrossRef21
Paul D. Miller. (2008) Non-vertebral fracture risk reduction with oral bisphosphonates: challenges with interpreting clinical trial data. Current Medical Research and Opinion 24:1, 107-119
CrossRef22
M. Mamdani, A. Kopp, G. Hawker. (2007) Hip fractures in users of first- vs. second-generation bisphosphonates. Osteoporosis International 18:12, 1595-1600
CrossRef23
Richard Eastell. (2007) Aromatase inhibitors and bone. The Journal of Steroid Biochemistry and Molecular Biology 106:1-5, 157-161
CrossRef24
Takuo Fujita, Hajime Orimo, Tetsuo Inoue, Kiyoshi Kaneda, Minoru Sakurai, Rikushi Morita, Kichizo Yamamoto, Yoichi Sugioka, Akio Inoue, Kunio Takaoka, Itsuo Yamamoto, Yuichi Hoshino, Hiroshi Kawaguchi. (2007) Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol. Journal of Bone and Mineral Metabolism 25:2, 130-137
CrossRef25
Richard Keen. (2007) Osteoporosis: strategies for prevention and management. Best Practice & Research Clinical Rheumatology 21:1, 109-122
CrossRef26
Lee S. Simon. (2007) Osteoporosis. Rheumatic Disease Clinics of North America 33:1, 149-176
CrossRef27
Jean-Yves Reginster, Olivier Malaise, Audrey Neuprez, Victor-Emmanuel Jouret, Pierre Close. (2007) Intermittent Bisphosphonate Therapy in Postmenopausal Osteoporosis. Drugs & Aging 24:5, 351-359
CrossRef28
Glen M. Blake, Ignac Fogelman. (2007) Role of Dual-Energy X-Ray Absorptiometry in the Diagnosis and Treatment of Osteoporosis. Journal of Clinical Densitometry 10:1, 102-110
CrossRef29
P. Fardellone. (2007) Interesse e limiti dei trattamenti antiosteoporotici. EMC - AKOS - Trattato di Medicina 9:4, 1-7
CrossRef30
Rachael L Fleurence, Cynthia P Iglesias, Jeanene M Johnson. (2007) The Cost Effectiveness of Bisphosphonates for the Prevention and Treatment of Osteoporosis. PharmacoEconomics 25:11, 913-933
CrossRef31
Yoshihiro Sato, Yoshiaki Honda, Jun Iwamoto. (2006) Etidronate for fracture prevention in amyotrophic lateral sclerosis: A randomized controlled trial. Bone 39:5, 1080-1086
CrossRef32
Atsufumi Kawabata, Naoyuki Kawao, Yoshimi Hironaka, Tsuyoshi Ishiki, Maho Matsunami, Fumiko Sekiguchi. (2006) Antiallodynic effect of etidronate, a bisphosphonate, in rats with adjuvant-induced arthritis: Involvement of ATP-sensitive K+ channels. Neuropharmacology 51:2, 182-190
CrossRef33
Philip Sambrook, Cyrus Cooper. (2006) Osteoporosis. The Lancet 367:9527, 2010-2018
CrossRef34
M. Sosa Henríquez, D. Hernández Hernández. (2006) Tratamiento de la osteoporosis. Medicine - Programa de Formación Médica Continuada Acreditado 9:60, 3880-3884
CrossRef35
J. K. Dhesi, T. J. Allain, A. A. Mangoni, S. H. D. Jackson. (2006) The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis. British Journal of Clinical Pharmacology 61:5, 521-528
CrossRef36
J. S. Bauer, D. Müller, A. Ambekar, M. Dobritz, M. Matsuura, F. Eckstein, E. J. Rummeny, T. M. Link. (2006) Detection of osteoporotic vertebral fractures using multidetector CT. Osteoporosis International 17:4, 608-615
CrossRef37
Nguyen D Nguyen, John A Eisman, Tuan V Nguyen. (2006) Anti-Hip Fracture Efficacy of Bisphosphonates: A Bayesian Analysis of Clinical Trials. Journal of Bone and Mineral Research 21:2, 340-349
CrossRef38
Jean-Yves Reginster, Dieter Felsenberg, Cyrus Cooper, Jacob A. Stakkestad, Paul D Miller, David L. Kendler, Silvano Adami, Michael R. McClung, Michael A. Bolognese, Roberto Civitelli, Etienne Dumont, Bernard Bonvoisin, Robert R Recker, Pierre D. Delmas. (2006) A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate. Osteoporosis International 17:2, 159-166
CrossRef39
Toshihiro Nakahara, Nobuatsu Nagai, Muneki Tanaka, Tetsuro Muranaga, Shinya Kojima, Shin-ichi Nozoe, Tetsuro Naruo. (2006) The effects of bone therapy on tibial bone loss in young women with anorexia nervosa. International Journal of Eating Disorders 39:1, 20-26
CrossRef40
2006. Bisphosphonates. , 523-527.
CrossRef41
S. K. Fokter, R. Komadina, A. Repše-Fokter, S. A. Yerby, A. Kocijančič, J. Marc. (2005) Etidronate does not suppress periprosthetic bone loss following cemented hip arthroplasty. International Orthopaedics 29:6, 362-367
CrossRef42
Juliet Compston. (2005) How to manage osteoporosis after the menopause. Best Practice & Research Clinical Rheumatology 19:6, 1007-1019
CrossRef43
Elisabeth J Smith, David G Little, Julie N Briody, Anthony McEvoy, Nicholas C Smith, John A Eisman, Edith M Gardiner. (2005) Transient Disturbance in Physeal Morphology Is Associated With Long-Term Effects of Nitrogen-Containing Bisphosphonates in Growing Rabbits. Journal of Bone and Mineral Research 20:10, 1731-1741
CrossRef44
Thomas M. Link, Giuseppe Guglielmi, Cornelis Kuijk, Judith E. Adams. (2005) Radiologic assessment of osteoporotic vertebral fractures: diagnostic and prognostic implications. European Radiology 15:8, 1521-1532
CrossRef45
L. Carreño Pérez. (2005) Tratamiento de la pérdida de masa ósea en la mujer postmenopáusica. Revista Clínica Española 205:7, 341-351
CrossRef46
Ghada El-Hajj Fuleihan, Rafic Baddoura, Hassane Awada, Jad Okais, Paul Rizk, Michael McClung. (2005) Lebanese Guidelines for Osteoporosis Assessment and Treatment. Journal of Clinical Densitometry 8:2, 148-163
CrossRef47
Jesse S. Siffledeen, Richard N. Fedorak, Kerry Siminoski, Ho Jen, Eric Vaudan, Neena Abraham, Hillary Steinhart, Gordon Greenberg. (2005) Randomized trial of etidronate plus calcium and vitamin D for treatment of low bone mineral density in Crohn’s disease. Clinical Gastroenterology and Hepatology 3:2, 122-132
CrossRef48
Soji Kasayama, Mari Fujita, Kayoko Goya, Hiroyasu Yamamoto, Kimie Fujita, Yasuhiko Morimoto, Ichiro Kawase, Akihiko Miyatake. (2005) Effects of alendronate on bone mineral density and bone metabolic markers in postmenopausal asthmatic women treated with inhaled corticosteroids. Metabolism 54:1, 85-90
CrossRef49
Marie-Paul Lecart, Olivier Bruyere, Jean-Yves Reginster. (2004) Combination/sequential therapy in osteoporosis. Current Osteoporosis Reports 2:4, 123-130
CrossRef50
Elisabeth J Smith, Anthony McEvoy, David G Little, Paul A Baldock, John A Eisman, Edith M Gardiner. (2004) Transient Retention of Endochondral Cartilaginous Matrix With Bisphosphonate Treatment in a Long-Term Rabbit Model of Distraction Osteogenesis. Journal of Bone and Mineral Research 19:10, 1698-1705
CrossRef51
E. Cauza, M. Etemad, F. Winkler, H. Hanusch-Enserer, G. Partsch, H. Noske, A. Dunky. (2004) Pamidronate increases bone mineral density in women with postmenopausal or steroid-induced osteoporosis. Journal of Clinical Pharmacy and Therapeutics 29:5, 431-436
CrossRef52
Kosaku Nitta, Takashi Akiba, Koichi Suzuki, Keiko Uchida, Ryo-Ichiro Watanabe, Kazuhiro Majima, Takanao Aoki, Hiroshi Nihei. (2004) Effects of cyclic intermittent etidronate therapy on coronary artery calcification in patients receiving long-term hemodialysis. American Journal of Kidney Diseases 44:4, 680-688
CrossRef53
Leena Vehmanen, Tiina Saarto, Juha Risteli, Leila Risteli, Carl Blomqvist, Inkeri Elomaa. (2004) Short-Term Intermittent Intravenous Clodronate in the Prevention of Bone Loss Related to Chemotherapy-Induced Ovarian Failure. Breast Cancer Research and Treatment 87:2, 181-188
CrossRef54
Charles H Chesnut, Arne Skag, Claus Christiansen, Robert Recker, Jacob A Stakkestad, Arne Hoiseth, Dieter Felsenberg, Hermann Huss, Jennifer Gilbride, Ralph C Schimmer, Pierre D Delmas. (2004) Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis. Journal of Bone and Mineral Research 19:8, 1241-1249
CrossRef55
Katsuyuki Yamaguchi, Kensaku Masuhara, Satoshi Yamasaki, Takeshi Fuji, Yoshiki Seino. (2004) Effects of discontinuation as well as intervention of cyclic therapy with etidronate on bone remodeling after cementless total hip arthroplasty. Bone 35:1, 217-223
CrossRef56
Gianluigi Poli, Fabrizia Mariotti, Mario Ermanno Corrado, Daniela Acerbi. (2004) A tolerability andpharmacokinetic study of a newinjectable formulation of disodium clodronate in healthyfemale volunteers. European Journal of Drug Metabolism and Pharmacokinetics 29:2, 145-152
CrossRef57
J.-Y. Reginster. (2004) Prevention of postmenopausal osteoporosis with pharmacological therapy: practice and possibilities. Journal of Internal Medicine 255:6, 615-628
CrossRef58
Kim T. Brixen, Brixen Christensen, Charlotte Ejersted, Bente Lomholt Langdahl. (2004) Teriparatide (Biosynthetic Human Parathyroid Hormone 1-34): A New Paradigm in the Treatment of Osteoporosis. Pharmacology and Toxicology 94:6, 260-270
CrossRef59
Yoshihiro Sato, Tomohiro Kanoko, Hajime Yasuda, Kei Satoh, Jun Iwamoto. (2004) Beneficial Effect of Etidronate Therapy in Immobilized Hip Fracture Patients. American Journal of Physical Medicine & Rehabilitation 83:4, 298-303
CrossRef60
Pierre D Delmas, Ego Seeman. (2004) Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone 34:4, 599-604
CrossRef61
S. S. Y. Chan, L. M. Nery, A. McElduff, E. G. Wilmshurst, G. R. Fulcher, B. G. Robinson, J. N. StIel, J. E. Gunton, P. B. Clifton-Bligh. (2004) Intravenous pamidronate in the treatment and prevention of osteoporosis. Internal Medicine Journal 34:4, 162-166
CrossRef62
Julian M. R. Mathoo, Ann Cranney, Alexandra Papaioannou, Jonathan D. Adachi. (2004) Rational use of oral bisphosphonates for the treatment of osteoporosis. Current Osteoporosis Reports 2:1, 17-23
CrossRef63
PD Delmas, Zhengqing Li, Cyrus Cooper. (2004) Relationship Between Changes in Bone Mineral Density and Fracture Risk Reduction With Antiresorptive Drugs: Some Issues With Meta-Analyses. Journal of Bone and Mineral Research 19:2, 330-337
CrossRef64
R.M. Francis. (2004) Acute and long-term management of patients with vertebral fractures. QJM 97:2, 63-74
CrossRef65
Margaret E Fadanelli, Henry G Bone. (2004) Combining Bisphosphonates with Hormone Therapy for Postmenopausal Osteoporosis. Treatments in Endocrinology 3:6, 361-369
CrossRef66
Stanley B. Cohen. (2004) An update on bisphosphonates. Current Rheumatology Reports 6:1, 59-65
CrossRef67
Garabed Eknoyan, Adeera Levin, Nathan W Levin. (2003) Bone metabolism and disease in chronic kidney disease. American Journal of Kidney Diseases 42, 1-201
CrossRef68
Nuria Guanabens, Albert Pares, Inmaculada Ros, Luisa Alvarez, Francesca Pons, Llorenc Caballeria, Ana Monegal, M. Jesus Martinez Osaba, Merce Roca, Pilar Peris, Juan Rodes. (2003) Alendronate is more effective than etidronate for increasing bone mass in osteopenic patients with primary biliary cirrhosis. The American Journal of Gastroenterology 98:10, 2268-2274
CrossRef69
Christian von Tirpitz, Max Reinshagen. (2003) Management of osteoporosis in patients with gastrointestinal diseases. European Journal of Gastroenterology & Hepatology 15:8, 869-876
CrossRef70
Ian R. Reid. (2003) Bisphosphonates: new indications and methods of administration. Current Opinion in Rheumatology 15:4, 458-463
CrossRef71
Katsuyuki Yamaguchi, Kensaku Masuhara, Satoshi Yamasaki, Tsuyoshi Nakai, Takeshi Fuji. (2003) Cyclic therapy with etidronate has a therapeutic effect against local osteoporosis after cementless total hip arthroplasty. Bone 33:1, 144-149
CrossRef72
E ROME. (2003) Eating disorders. Obstetrics and Gynecology Clinics of North America 30:2, 353-377
CrossRef73
Michael R McClung. (2003) Bisphosphonates. Endocrinology & Metabolism Clinics of North America 32:1, 253-271
CrossRef74
Satoshi Komatsubara, Satoshi Mori, Tasuku Mashiba, Masako Ito, Jiliang Li, Yoshio Kaji, Tomoyuki Akiyama, Kensaku Miyamoto, Yongping Cao, Jun Kawanishi, Hiromichi Norimatsu. (2003) Long-Term Treatment of Incadronate Disodium Accumulates Microdamage but Improves the Trabecular Bone Microarchitecture in Dog Vertebra. Journal of Bone and Mineral Research 18:3, 512-520
CrossRef75
Zhengqing Li, Michael P. Meredith. (2003) Exploring the Relationship Between Surrogates and Clinical Outcomes: Analysis of Individual Patient Data vs. Meta-regression on Group-Level Summary Statistics. Journal of Biopharmaceutical Statistics 13:4, 777-792
CrossRef76
S.Y Smith, R.R Recker, M Hannan, R Müller, F Bauss. (2003) Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys. Bone 32:1, 45-55
CrossRef77
S. Nuzzo, M. H. Lafage-Proust, E. Martin-Badosa, G. Boivin, T. Thomas, C. Alexandre, F. Peyrin. (2002) Synchrotron Radiation Microtomography Allows the Analysis of Three-Dimensional Microarchitecture and Degree of Mineralization of Human Iliac Crest Biopsy Specimens: Effects of Etidronate Treatment. Journal of Bone and Mineral Research 17:8, 1372-1382
CrossRef78
Howard C. Tenenbaum, Avi Shelemay, Bruno Girard, Ron Zohar, Peter C. Fritz. (2002) Bisphosphonates and Periodontics: Potential Applications for Regulation of Bone Mass in the Periodontium and Other Therapeutic/ Diagnostic Uses. Journal of Periodontology 73:7, 813-822
CrossRef79
Pierre D Delmas. (2002) Treatment of postmenopausal osteoporosis. The Lancet 359:9322, 2018-2026
CrossRef80
Caroline Brumsen, Socrates E. Papapoulos, Paul Lips, Petronella H. L. M. Geelhoed-Duijvestijn, Neveen A. T. Hamdy, Jan Otto Landman, Eugene V. Mccloskey, J. Coen Netelenbos, Ernest K. J. Pauwels, Jan C. Roos, Rob M. Valentijn, Aeilko H. Zwinderman. (2002) Daily Oral Pamidronate in Women and Men With Osteoporosis: A 3-Year Randomized Placebo-Controlled Clinical Trial With a 2-Year Open Extension. Journal of Bone and Mineral Research 17:6, 1057-1064
CrossRef81
Daphne J. Theodorou, Stavroula J. Theodorou, David J. Sartoris. (2002) Treatment of osteoporosis: Current status and recent advances. Comprehensive Therapy 28:2, 109-122
CrossRef82
Reid, Ian R., Brown, Jacques P., Burckhardt, Peter, Horowitz, Zebulun, Richardson, Peter, Trechsel, Ulrich, Widmer, Albert, Devogelaer, Jean-Pierre, Kaufman, Jean-Marc, Jaeger, Philippe, Body, Jean-Jacques, Brandi, Maria Luisa, Broell, Johann, Di Micco, Raffaele, Genazzani, Andrea Riccardo, Felsenberg, Dieter, Happ, Joachim, Hooper, Michael J., Ittner, Jochen, Leb, Georg, Mallmin, Hans, Murray, Timothy, Ortolani, Sergio, Rubinacci, Alessandro, Sääf, Maria, Samsioe, Goran, Verbruggen, Leon, Meunier, Pierre J., . (2002) Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral Density. New England Journal of Medicine 346:9, 653-661
Full Text83
Gregory R. Mundy. (2002) D
IRECTIONS OF DRUG DISCOVERY IN OSTEOPOROSIS . Annual Review of Medicine 53:1, 337-354
CrossRef84
J Iwamoto, T Takeda, T Katsumata, T Tanaka, S Ichimura, Y Toyama. (2002) Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats. Bone 30:2, 360-367
CrossRef85
S. H. Gehlbach, M. Fournier, C. Bigelow. (2002) Recognition of Osteoporosis by Primary Care Physicians. American Journal of Public Health 92:2, 271-273
CrossRef86
Philip C. Bulman Page, Michael J. McKenzie, James A. Gallagher. (2002) SIMPLE SYNTHESIS OF OXIRANYLIDENE-2,2- BIS (PHOSPHONIC ACID): TETRABENZYL GEMINAL BISPHOSPHONATE ESTERS AS USEFUL INTERMEDIATES. Synthetic Communications 32:2, 211-218
CrossRef87
G.E Piérard, S Vanderplaetsen, C Piérard-Franchimont. (2001) Comparative effect of hormone replacement therapy on bone mass density and skin tensile properties. Maturitas 40:3, 221-227
CrossRef88
Bernard Cortet, Anne Béra-Louville, Patrick Gauthier, Alain Gauthier, Xavier Marchandise, Bernard Delcambre. (2001) Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. Effect of adding hormone replacement therapy. Joint Bone Spine 68:5, 410-415
CrossRef89
Tricia Woo, Jonathan D. Adachi. (2001) Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis. Best Practice & Research Clinical Rheumatology 15:3, 469-481
CrossRef90
M Ito, N Amizuka, T Nakajima, H Ozawa. (2001) Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic (oc/oc) mice. Bone 28:6, 609-616
CrossRef91
Neer, Robert M.Arnaud, Claude D.Zanchetta, Jose R.Prince, RichardGaich, Gregory A.Reginster, Jean-YvesHodsman, Anthony B.Eriksen, Erik F.Ish-Shalom, SophiaGenant, Harry K.Wang, OuhongMellström, DanOefjord, Erik S.Marcinowska-Suchowierska, EwaSalmi, JormaMulder, HenkHalse, JohanSawicki, Andrzej Z.Mitlak, Bruce H.. (2001) Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis. New England Journal of Medicine 344:19, 1434-1441
Full Text92
E.M. Hauge, Le. Mosekilde, F. Melsen, M. Frydenberg. (2001) How many patients are needed? Variation and design considerations in bone histomorphometry. Bone 28:5, 556-562
CrossRef93
E Samnegård, M.P Akhter, R.R Recker. (2001) Maintenance of vertebral body bone mass and strength created by human parathyroid hormone treatment in ovariectomized rats. Bone 28:4, 414-422
CrossRef94
Chaoyang Li, Satoshi Mori, Jiliang Li, Yoshio Kaji, Tomoyuki Akiyama, Jun Kawanishi, Hiromichi Norimatsu. (2001) Long-Term Effect of Incadronate Disodium (YM-175) on Fracture Healing of Femoral Shaft in Growing Rats. Journal of Bone and Mineral Research 16:3, 429-436
CrossRef95
Nelson B. Watts. (2001) Treatment of Osteoporosis with Bisphosphonates. Rheumatic Disease Clinics of North America 27:1, 197-214
CrossRef96
Douglas Coyle, Ann Cranney, Karen M. Lee, Vivian Welch, Peter Tugwell. (2001) Cost Effectiveness of Nasal Calcitonin in Postmenopausal Women. PharmacoEconomics 19:Parts 1 and 2, 565-575
CrossRef97
Hideki Hirabayashi, Toshiya Takahashi, Jiro Fujisaki, Taro Masunaga, Sachio Sato, Jun Hiroi, Yuji Tokunaga, Sumihisa Kimura, Takehisa Hata. (2001) Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS). Journal of Controlled Release 70:1-2, 183-191
CrossRef98
Christopher J. Dunn, Karen L. Goa. (2001) Risedronate. Drugs 61:5, 685-712
CrossRef99
Yoshihiro Sato, Takeshi Asoh, Masahide Kaji, Kotaro Oizumi. (2000) Beneficial Effect of Intermittent Cyclical Etidronate Therapy in Hemiplegic Patients Following an Acute Stroke. Journal of Bone and Mineral Research 15:12, 2487-2494
CrossRef100
T Nishikawa, S Ogawa, K Kogita, N Manabe, T Katsumata, K Nakamura, H Kawaguchi. (2000) Additive effects of combined treatment with etidronate and alfacalcidol on bone mass and mechanical properties in ovariectomized rats. Bone 27:5, 647-654
CrossRef101
Ivar Aursnes MD, Geir Storvik PhD, J
rund G
CrossRef102
Jiliang Li, Satoshi Mori, Yoshio Kaji, Jun Kawanishi, Tomoyuki Akiyama, Hiromichi Norimatsu. (2000) Concentration of Bisphosphonate (Incadronate) in Callus Area and Its Effects on Fracture Healing in Rats. Journal of Bone and Mineral Research 15:10, 2042-2051
CrossRef103
M. A. H Levine, P Grootendorst. (2000) Proportion of osteoporotic post-menopausal women at increased risk for upper GI adverse events associated with bisphosphonate therapy. Pharmacoepidemiology and Drug Safety 9:5, 367-370
CrossRef104
Philip Sambrook, N. Kathy Henderson, Anne Keogh, Peter MacDonald, Allan Glanville, Phillip Spratt, Peter Bergin, Peter Ebeling, John Eisman. (2000) Effect of Calcitriol on Bone Loss After Cardiac or Lung Transplantation. Journal of Bone and Mineral Research 15:9, 1818-1824
CrossRef105
Anne M. Kenny, Karen M. Prestwood. (2000) OSTEOPOROSIS. Rheumatic Disease Clinics of North America 26:3, 569-591
CrossRef106
W Andrews. (2000) Prevention and Treatment of Osteoporosis. ACOG Clinical Review 5:4, 1
CrossRef107
Frank H.J Wolfhagen, Henk R van Buuren, Frank P Vleggaar, Solko W Schalm. (2000) Management of osteoporosis in primary biliary cirrhosis. Best Practice & Research Clinical Gastroenterology 14:4, 629-641
CrossRef108
T Hirano, C.H Turner, M.R Forwood, C.C Johnston, D.B Burr. (2000) Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation?. Bone 27:1, 13-20
CrossRef109
N Guañabens, J Farrerons, L Perez-Edo, A Monegal, A Renau, J Carbonell, M Roca, M Torra, M Pavesi. (2000) Cyclical etidronate versus sodium fluoride in established postmenopausal osteoporosis: a randomized 3 year trial. Bone 27:1, 123-128
CrossRef110
M Rossini, D Gatti, S Girardello, V Braga, G James, S Adami. (2000) Effects of two intermittent alendronate regimens in the prevention or treatment of postmenopausal osteoporosis. Bone 27:1, 119-122
CrossRef111
Ego Seeman. (2000) Selection of individuals for prevention of fractures due to bone fragility. Best Practice & Research Clinical Endocrinology & Metabolism 14:2, 233-249
CrossRef112
Sunil J. Wimalawansa. (2000) Prevention and Treatment of Osteoporosis: Efficacy of Combination of Hormone Replacement Therapy with Other Antiresorptive Agents. Journal of Clinical Densitometry 3:2, 187-201
CrossRef113
Juliet Compston. (2000) Prevention of osteoporotic fractures in post-menopausal women. Best Practice & Research Clinical Endocrinology & Metabolism 14:2, 251-264
CrossRef114
D.A. Heath, B.G. Bullivant, C. Boiven, R. Balena. (2000) The Effects of Cyclical Etidronate on Early Postmenopausal Bone Loss. Journal of Clinical Densitometry 3:1, 27-33
CrossRef115
David A. Hanley, George Ioannidis, J.D. (Rick) Adachi. (2000) Etidronate Therapy in the Treatment and Prevention of Osteoporosis. Journal of Clinical Densitometry 3:1, 79-95
CrossRef116
Pauline Boulos, George Ioannidis, Jonathan D. Adachi. (2000) Glucocorticoid-induced osteoporosis. Current Rheumatology Reports 2:1, 53-61
CrossRef117
Jonathan D. Adachi, Wojciech P. Olszynski, David A. Hanley, Anthony B. Hodsman, David L. Kendler, Kerry G. Siminoski, Jacques Brown, Elizabeth A. Cowden, David Goltzman, George Ioannidis, Robert G. Josse, Louis-Georges Ste-Marie, Alan M. Tenenhouse, K. Shawn Davison, Ken L.N. Blocka, A. Patrice Pollock, John Sibley. (2000) Management of corticosteroid-induced osteoporosis. Seminars in Arthritis and Rheumatism 29:4, 228-251
CrossRef118
Sategna-Guidetti, Grosso, Grosso, Mengozzi, Aimo, Zaccaria, Di Stefano, Isaia. (2000) The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients. Alimentary Pharmacology and Therapeutics 14:1, 35-43
CrossRef119
Henry G. Bone, Silvano Adami, Rene Rizzoli, Murray Favus, Philip D. Ross, Arthur Santora, Srinivasa Prahalada, Anastasia Daifotis, John Orloff, John Yates. (2000) Weekly administration of alendronate: Rationale and plan for clinical assessment. Clinical Therapeutics 22:1, 15-28
CrossRef120
Yasufumi Ichinose, Kiyoshi Migita, Tomoki Nakashima, Atsushi Kawakami, Takahiko Aoyagi, Katsumi Eguchi. (2000) Effects of Bisphosphonate on the Release of MMP-2 from Cultured Human Osteoblasts. The Tohoku Journal of Experimental Medicine 192:2, 111-118
CrossRef121
Alison Stewart, Leslie G. Walker, Richard W. Porter, David M. Reid, William R. Primrose. (1999) Predicting a Second Hip Fracture. Journal of Clinical Densitometry 2:4, 363-370
CrossRef122
Robert D. Blank, Richard S. Bockman. (1999) A Review of Clinical Trials of Therapies for Osteoporosis Using Fracture as an End Point. Journal of Clinical Densitometry 2:4, 435-452
CrossRef123
S Kobayashi, T Shimizu, R Mehdi, M Nawata, S Kojima, T Tsutsumimoto, R Iorio, K Takaoka. (1999) Advantages of concurrent use of anabolic and antiresorptive agents over single use of these agents in increasing trabecular bone volume, connectivity, and biomechanical competence of rat vertebrae. Bone 25:6, 703-712
CrossRef124
M.C Nevitt, P.D Ross, L Palermo, T Musliner, H.K Genant, D.E Thompson. (1999) Association of prevalent vertebral fractures, bone density, and alendronate treatment with incident vertebral fractures: effect of number and spinal location of fractures. Bone 25:5, 613-619
CrossRef125
R. Graham G. Russell, Michael J. Rogers, Julie C. Frith, Steven P. Luckman, Fraser P. Coxon, Helena L. Benford, Peter I. Croucher, Claire Shipman, Herbert A. Fleisch. (1999) The pharmacology of bisphosphonates and new insights into their mechanisms of action. Journal of Bone and Mineral Research 14:S2, 53-65
CrossRef126
N. Patlas, G. Golomb, P. Yaffe, T. Pinto, E. Breuer, A. Ornoy. (1999) Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats. Teratology 60:2, 68-73
CrossRef127
R.G.G Russell, M.J Rogers. (1999) Bisphosphonates: from the laboratory to the clinic and back again. Bone 25:1, 97-106
CrossRef128
Jiliang Li, Satoshi Mori, Yoshio Kaji, Tasuku Mashiba, Jun Kawanishi, Hiromichi Norimatsu. (1999) Effect of Bisphosphonate (Incadronate) on Fracture Healing of Long Bones in Rats. Journal of Bone and Mineral Research 14:6, 969-979
CrossRef129
Toru Hirano, David B. Burr, Charles H. Turner, Masahiko Sato, Rick L. Cain, Janet M. Hock. (1999) Anabolic Effects of Human Biosynthetic Parathyroid Hormone Fragment (1-34), LY333334, on Remodeling and Mechanical Properties of Cortical Bone in Rabbits. Journal of Bone and Mineral Research 14:4, 536-545
CrossRef130
Thierry Thomas, Odile Barou, Laurence Vico, Christian Alexandre, Marie-Helene Lafage-Proust. (1999) Recurrence of Vertebral Fracture with Cyclical Etidronate Therapy in Osteoporosis: Histomorphometry and X-Ray Microanalysis Evaluation. Journal of Bone and Mineral Research 14:2, 198-205
CrossRef131
M Rossini, V Braga, D Gatti, D Gerardi, N Zamberlan, S Adami. (1999) Intramuscular clodronate therapy in postmenopausal osteoporosis. Bone 24:2, 125-129
CrossRef132
R. Graham, G. Russell. (1999) The Bisphosphonate Odyssey. A Journey from Chemistry to the Clinic. Phosphorus, Sulfur, and Silicon and the Related Elements 144:1, 793-820
CrossRef133
Dennis M. Black, Lisa Palermo, Michael C. Nevitt, Harry K. Genant, Lisa Christensen, Steven R. Cummings. (1999) Defining Incident Vertebral Deformity: A Prospective Comparison of Several Approaches. Journal of Bone and Mineral Research 14:1, 90-101
CrossRef134
Piet Geusens, Steven Boonen. (1998) Risk Assessment for Osteoporosis Using Bone Mineral Density Determination. Journal of Clinical Densitometry 1:4, 355-358
CrossRef135
Steven P. Luckman, Fraser P. Coxon, Frank H. Ebetino, R. Graham G. Russell, Michael J. Rogers. (1998) Heterocycle-Containing Bisphosphonates Cause Apoptosis and Inhibit Bone Resorption by Preventing Protein Prenylation: Evidence from Structure-Activity Relationships in J774 Macrophages. Journal of Bone and Mineral Research 13:11, 1668-1678
CrossRef136
Paola Albertazzi, Raffaele Di Micco, Ettore Zanardi. (1998) Tibolone: a review. Maturitas 30:3, 295-305
CrossRef137
J. M. S. Macedo, C. R. B. Macedo, H. Elkis, I. R. De Oliveira. (1998) Meta-analysis about efficacy of anti-resorptive drugs in post-menopausal osteoporosis. Journal of Clinical Pharmacy and Therapeutics 23:5, 345-352
CrossRef138
Johann D. Ringe. (1998) The interpretation of preclinical data in predicting bisphosphonate response in the treatment of osteoporosis. Clinical Therapeutics 20:4, 648-660
CrossRef139
Haruhiko Tokuda, Osamu Kozawa, Atsushi Harada, Toshihiko Uematsu. (1998) Tiludronate inhibits interleukin-6 synthesis in osteoblasts: Inhibition of phospholipase D activation in MC3T3-E1 cells. Journal of Cellular Biochemistry 69:3, 252-259
CrossRef140
P Ravn, J.O Christensen, M Baumann, B Clemmesen. (1998) Changes in Biochemical Markers and Bone Mass After Withdrawal of Ibandronate Treatment: Prediction of Bone Mass Changes During Treatment. Bone 22:5, 559-564
CrossRef141
A. Pickersgill. (1998) GnRH agonists and add-back therapy: is there a perfect combination?. BJOG: An International Journal of Obstetrics and Gynaecology 105:5, 475-485
CrossRef142
Brian D. Golden. (1998) The prevention and treatment of osteoporosis. Arthritis Care & Research 11:2, 124-134
CrossRef143
Wei Qing Wang, Mary Sau Man Ip, Kenneth Wau Tak Tsang, Karen Siu Ling Lam. (1998) Antiresorptive therapy in asthmatic patients receiving high-dose inhaled steroids: A prospective study for 18 months. Journal of Allergy and Clinical Immunology 101:4, 445-450
CrossRef144
Wood, Alastair J.J., , Eastell, Richard, . (1998) Treatment of Postmenopausal Osteoporosis. New England Journal of Medicine 338:11, 736-746
Full Text145
Hosking, David, Chilvers, Clair E.D., Christiansen, Claus, Ravn, Pernille, Wasnich, Richard, Ross, Philip, McClung, Michael, Balske, Ana, Thompson, Desmond, Daley, Marianne, Yates, A. John, . (1998) Prevention of Bone Loss with Alendronate in Postmenopausal Women under 60 Years of Age. New England Journal of Medicine 338:8, 485-492
Full Text146
A. John Yates, Gideon A. Rodan. (1998) Alendronate and osteoporosis. Drug Discovery Today 3:2, 69-78
CrossRef147
K. Brixen, T.B. Hansen, E.F. Eriksen, L. Mosekilde. (1998) Does growth hormone therapy in adult patients with growth hormone deficiency protect against bone loss?. Growth Hormone & IGF Research 8, 81-86
CrossRef148
Karl J Obrant. (1998) Prevention of osteoporotic fractures-should orthopedic surgeons care?. Acta Orthopaedica 69:4, 333-338
CrossRef149
Jan E Madsen, Trine Berg-larsen, Ole J Kirkeby, Jan A Falch, Lars Nordsletten. (1998) No adverse effects of clodronate on fracture healing in rats. Acta Orthopaedica 69:5, 532-536
CrossRef150
(1997) Intermittent Etidronate and Corticosteroid-Induced Osteoporosis. New England Journal of Medicine 337:26, 1921-1921
Full Text151
Joseph E. Zerwekh, Peter P. Antich, Shreefal Mehta, Khashayar Sakhaee, Frank Gottschalk, Charles Y. C. Pak. (1997) Reflection Ultrasound Velocities and Histomorphometric and Connectivity Analyses: Correlations and Effect of Slow-Release Sodium Fluoride. Journal of Bone and Mineral Research 12:12, 2068-2075
CrossRef152
E.N. Ebbesen, J.S. Thomsen, Li. Mosekilde. (1997) Nondestructive determination of iliac crest cancellous bone strength by pQCT. Bone 21:6, 535-540
CrossRef153
Liu Zhang, Hideaki E. Takahashi, Tatsuhiko Tanizawa, Naoto Endo, Noriaki Yamamoto. (1997) Maintenance of bone mineral density of femoral cortex in ovariectomized rats after withdrawal of concurrent administration of human parathyroid hormone (1–34) and incardronate disodium (YM175). Journal of Bone and Mineral Metabolism 15:4, 206-212
CrossRef154
Joseph M. Lane. (1997) Osteoporosis. Spine 22:Supplement, 32S-37S
CrossRef155
Clifford J Rosen. (1997) A tale of two worlds in prescribing etidronate for osteoporosis. The Lancet 350:9088, 1340
CrossRef156
Allan Lipton. (1997) Bisphosphonates and breast carcinoma. Cancer 80:S8, 1668-1673
CrossRef157
D Thiébaud, P Burckhardt, H Kriegbaum, H Huss, H Mulder, J.R Juttmann, K.H Schöter. (1997) Three Monthly Intravenous Injections of Ibandronate in the Treatment of Postmenopausal Osteoporosis. The American Journal of Medicine 103:4, 298-307
CrossRef158
Daniel L. Hurley, Sundeep Khosla. (1997) Update on Primary Osteoporosis. Mayo Clinic Proceedings 72:10, 943-949
CrossRef159
Caro Brumsen, Neveen A. T. Hamdy, Socrates E. Papapoulos. (1997) Long-Term Effects of Bisphosphonates on the Growing Skeleton. Medicine 76:4, 266-283
CrossRef160
G. P. Lyritis, N. Tsakalakos, I. Paspati, Gr. Skarantavos, A. Galanos, C. Androulakis. (1997) The effect of a modified etidronate cyclical regimen on postmenopausal osteoporosis: A four-year study. Clinical Rheumatology 16:4, 354-360
CrossRef161
Hiroyuki Motoie, Atsushi Okazaki, Hiroyuki Kanoh, Hisataka Shikama, Takashi Fujikura. (1997) Increase of Bone Mass and Mechanical Strength in Rats after Treatment with a Novel Bisphosphonate, YM175, for Two Years. Pharmacology & Toxicology 81:1, 42-47
CrossRef162
Jane Marie Owens, Karen Fuller, Timothy John Chambers. (1997) Osteoclast activation: Potent inhibition by the bisphosphonate alendronate through a nonresorptive mechanism. Journal of Cellular Physiology 172:1, 79-86
CrossRef163
Li. Mosekilde, J.S. Thomsen, J.E. McOsker. (1997) No loss of biomechanical effects after withdrawal of short-term PTH treatment in an aged, osteopenic, ovariectomized rat model. Bone 20:5, 429-437
CrossRef164
J. M. Cardona, E. Pastor. (1997) Calcitonin versus etidronate for the treatment of postmenopausal osteoporosis: A meta-analysis of published clinical trials. Osteoporosis International 7:3, 165-174
CrossRef165
S. Adami, L. Bufalino, R. Cervetti, C. Marco, O. Munno, L. Fantasia, G. C. Isaia, U. Serni, L. Vecchiet, M. Passeri. (1997) Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporosis International 7:2, 119-125
CrossRef166
Angelo A. Licata. (1997) Bisphosphonate Therapy. The American Journal of the Medical Sciences 313:1, 17-22
CrossRef167
Herbert A. Fleisch. (1997) Bisphosphonates: Preclinical Aspects and Use in Osteoporosis. Annals of Medicine 29:1, 55-62
CrossRef168
G.S. Kim, C.-H. Kim, J.Y. Park, K.-U. Lee, C.S. Park. (1996) Effects of vitamin B12 on cell proliferation and cellular alkaline phosphatase activity in human bone marrow stromal osteoprogenitor cells and UMR106 osteoblastic cells. Metabolism 45:12, 1443-1446
CrossRef169
C. Parker, D. Hosking. (1996) Treatment of osteoporosis: bisphosphonates as an alternative to hormone replacement therapy. Current Obstetrics & Gynaecology 6:4, 206-211
CrossRef170
P. Ravn, B. Clemmesen, B.J. Riis, Christiansen C.. (1996) The effect on bone mass and bone markers of different doses of ibandronate: A new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: A 1-year, randomized, double-blind, placebo-controlled dose-finding study. Bone 19:5, 527-533
CrossRef171
J.S. Thomsen, Li. Mosekilde, E. Mosekilde. (1996) Quantification of remodeling parameter sensitivity—assessed by a computer simulation model. Bone 19:5, 505-511
CrossRef172
Michael J. Rogers, Kattya M. Chilton, Fraser P. Coxon, John Lawry, M. Olivia Smith, Sunita Suri, R. Graham G. Russel. (1996) Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism. Journal of Bone and Mineral Research 11:10, 1482-1491
CrossRef173
Vesa T. Lepola, Katriina Kippo, Ritva Hannuniemi, Leena Laurén, Teija Virtamo, Thua Österman, Pekka Jalovaara, Raija Sellman, H. Kalervo Väänänen. (1996) Bisphosphonates clodronate and etidronate in the prevention of ovariectomy-induced osteopenia in growing rats. Journal of Bone and Mineral Research 11:10, 1508-1517
CrossRef174
B. Berning, C.V. Kuijk, J.W. Kuiper, H.J.T. Coelingh Bennink, P.M. Kicovic, B.C.J.M. Fauser. (1996) Effects of two doses of tibolone on trabecular and cortical bone loss in early postmenopausal women: A two-year randomized, placebo-controlled study. Bone 19:4, 395-399
CrossRef175
Anne Peretz, Jean Jacques Body, Jean Claude Dumon, Serge Rozenberg, Anouk Hotimski, Jean Philippe Praet, Muriel Moris, Humphrey Ham, Pierre Bergmann. (1996) Cyclical pamidronate infusions in postmenopausal osteoporosis. Maturitas 25:1, 69-75
CrossRef176
T. Mukherjee, D. Barad, R. Turk, R. Freeman. (1996) A randomized, placebo-controlled study on the effect of cyclic intermittent etidronate therapy on the bone mineral density changes associated with six months of gonadotropin-releasing hormone agonist treatment. American Journal of Obstetrics and Gynecology 175:1, 105-109
CrossRef177
M. C. Ellerington, T. C. Hillard, S. I. J. Whitcroft, M. S. Marsh, B. Lees, L. M. Banks, M. I. Whitehead, J. C. Stevenson. (1996) Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis. Calcified Tissue International 59:1, 6-11
CrossRef178
Harry K. Genant, Michael Jergas, Lisa Palermo, Michael Nevitt, Ria San Valentin, Dennis Black, Steven R. Cummings. (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. Journal of Bone and Mineral Research 11:7, 984-996
CrossRef179
Roman M. Kowalchuk&NA;, Thomas A. Corcoran, Solomon R. Pollack, Marvin E. Steinberg. (1996) Effects of Etidronate and Oophorectomy on the Zeta Potential of Rat Bone. Clinical Orthopaedics and Related Research 328, 241-249
CrossRef180
R Rizzoli. (1996) Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer. Bone 18:6, 531-537
CrossRef181
Harry K. Genant, Klaus Engelke, Thomas Fuerst, Claus-C. Glüer, Stephan Grampp, Steven T. Harris, Michael Jergas, Thomas Lang, Ying Lu, Sharmila Majumdar, Ashwini Mathur, Masa Takada. (1996) Noninvasive assessment of bone mineral and structure: State of the art. Journal of Bone and Mineral Research 11:6, 707-730
CrossRef182
J.A. Kanis, E.V. McCloskey, M.N.C. Beneton. (1996) Clodronate and osteoporosis. Maturitas 23, S81-S86
CrossRef183
C.Y.C. Pak, A. Ho, J. Poindexter, R. Peterson, K. Sakhaee. (1996) Quantitation of incident spinal fractures: comparison of visual detection with quantitative morphometry. Bone 18:4, 349-353
CrossRef184
B.L. Riggs, L.J. Melton, W.M. O'Fallon. (1996) Drug therapy for vertebral fractures in osteoporosis: Evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone 18:3, S197-S201
CrossRef185
R. Ziegler, C. Scheidt-Nave, G. Leidig-Bruckner. (1996) What is a vertebral fracture?. Bone 18:3, S169-S177
CrossRef186
R. W. Keen, T. D. Spector. (1996) Role and evolution of therapeutic options. Osteoporosis International 6:S2, 16-20
CrossRef187
John D. Wark. (1996) Osteoporotic fractures: background and prevention strategies. Maturitas 23:2, 193-207
CrossRef188
P. Filipponi, S. Cristallini, E. Rizzello, G. Policani, L. Fedeli, F. Gregorio, S. Boldrini, S. Troiani, C. Massoni. (1996) Cyclical intravenous clodronate in postmenopausal osteoporosis: Results of a long-term Clinical trial. Bone 18:2, 179-184
CrossRef189
A. Sauty, M. Pecherstorfer, I. Zimmer-Roth, P. Fioroni, L. Juillerat, M. Markert, H. Ludwig, P. Leuenberger, P. Burckhardt, D. Thiébaudi. (1996) Interleukin-6 and tumor necrosis factor α levels after bisphosphonates treatment in vitro and in patients with malignancy. Bone 18:2, 133-139
CrossRef190
O. H. Sorensen, J-E. B. Jensen, G. Kollerup, H. A. Sorensen, L. B. Jensen. (1996) To Screen or not to Screen?. Scandinavian Journal of Rheumatology 25:s103, 25-29
CrossRef191
K. Kippo, R. Hannuniemi, T. Virtamo, L. Laurén, H. Ikävalko, V. Kovanen, T. Osterman, R. Sellman. (1995) The effects of clodronate on increased bone turnover and bone loss due to ovariectomy in rats. Bone 17:6, 533-542
CrossRef192
S.D. Vasikaran, S. Khan, E.V. McCloskey, J.A. Kanis. (1995) Sustained response to intravenous alendronate in postmenopausal osteoporosis. Bone 17:6, 517-520
CrossRef193
Liberman, Uri A., Weiss, Stuart R., Bröll, Johann, Minne, Helmut W., Quan, Hui, Bell, Norman H., Rodriguez-Portales, Jose, Downs, Robert W. Jr., Dequeker, Jan, Favus, Murray, Seeman, Ego, Recker, Robert R., Capizzi, Thomas, Santora, Arthur C., Lombardi, Antonio, Shah, Raksha V., Hirsch, Laurence J., Karpf, David B., . (1995) Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis. New England Journal of Medicine 333:22, 1437-1444
Full Text194
R. J. Erdtsieck, H. A. P. Pols, N. K. Valk, B. M. Ouwerkerk, S. W. J. Lamberts, P. Mulder, J. C. Birkenhäger. (1995) Treatment of post-menopausal osteoporosis with a combination of growth hormone and pamidronate: a placebo controlled trial. Clinical Endocrinology 43:5, 557-565
CrossRef195
David E. Hughes, Kenneth R. Wright, Harry L. Uy, Akira Sasaki, Toshiyuki Yoneda, David G. Roodman, Gregory R. Mundy, Brendan F. Boyce. (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. Journal of Bone and Mineral Research 10:10, 1478-1487
CrossRef196
Nancy E. Lane, J.M. Thompson, Gordon J. Strewler, J.H. Kinney. (1995) Intermittent treatment with human parathyroid hormone (hPTH[1-34]) increased trabecular bone volume but not connectivity in osteopenic rats. Journal of Bone and Mineral Research 10:10, 1470-1477
CrossRef197
F. P. Cantatore, M. Carrozzo. (1995) Treatment of osteoporosis of rheumatoid arthritis. Clinical Rheumatology 14:5, 594-595
CrossRef198
Barry J. Gertz, Sherry D. Holland, Walter F. Kline, Bogdan K. Matuszewski, Amanda Freeman, Hui Quan, Kenneth C. Lasseter, John C. Mucklow, Arturo G. Porras. (1995) Studies of the oral bioavailability of alendronate*. Clinical Pharmacology & Therapeutics 58:3, 288-298
CrossRef199
C. Y. Wu, J. Li, M. Jergas, H. K. Genant. (1995) Comparison of semiquantitative and quantitative techniques for the assessment of prevalent and incident vertebral fractures. Osteoporosis International 5:5, 354-370
CrossRef200
J. -Y. Reginster. (1995) The role of bisphosphonates in the prevention and treatment of osteoporosis. Clinical Rheumatology 14:S3, 22-25
CrossRef201
Felicia Cosman, Jeri Nieves, Jesus Walliser, Robert Lindsay. (1995) Postmenopausal osteoporosis: patient choices and outcomes. Maturitas 22:2, 137-143
CrossRef202
E. Seeman, C. Tsalamandris, S. Bass, G. Pearce. (1995) Present and future of osteoporosis therapy. Bone 17:2, S23-S29
CrossRef203
Torben Steiniche. (1995) Bone histomorphometry in the pathophysiological evaluation of primary and secondary osteoporosis and various treatment modalities. APMIS 103:S51, 5-44
CrossRef204
B. J. Riis, K. Overgaard, C. Christiansen. (1995) Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy. Osteoporosis International 5:4, 276-280
CrossRef205
M.R. Forwood, D.B. Burr, Y. Takano, D.F. Eastman, P.N. Smith, J.D. Schwardt. (1995) Risedronate treatment does not increase microdamage in the canine femoral neck. Bone 16:6, 643-650
CrossRef206
Takashi Katsumata, Toshitaka Nakamura, Hideo Ohnishi, Teruo Sakurama. (1995) Intermittent cyclical etidronate treatment maintains the mass, structure and the mechanical property of bone in ovariectomized rats. Journal of Bone and Mineral Research 10:6, 921-931
CrossRef207
RICHARD EASTELL, . (1995) Management of corticosteroid-induced osteoporosis. Journal of Internal Medicine 237:5, 439-447
CrossRef208
Paolo Filipponi, Mariano Pedetti, Leone Fedeli, Luisella Cini, Renato Palumbo, Stefano Boldrini, Cristina Massoni, Sonia Cristallini. (1995) Cyclical clodronate is effective in preventing postmenopausal bone loss: A comparative study with transcutaneous hormone replacement therapy. Journal of Bone and Mineral Research 10:5, 697-703
CrossRef209
Steven R.. (1995) Report assessing vertebral fractures. Journal of Bone and Mineral Research 10:4, 518-523
CrossRef210
A. Goziotis, B. Sukhu, M. Torontali, M. Dowhaniuk, H.C. Tenenbaum. (1995) Effects of bisphosphonates APD and HEBP on bone metabolism in vitro. Bone 16:4, S317-S327
CrossRef211
Y.F. Ma, W.S.S. Jee, H.Z. Ke, B.Y. Lin, X.G. Liang, M. Li, N. Yamamoto. (1995) Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats. Journal of Bone and Mineral Research 10:3, 496-505
CrossRef212
Tasuku Mashiba, Tatsuhiko Tanizawa, Hideaki E. Takahashi, Yuichi Takano, Saburo Nishida, Satoshi Mori, Hiromichi Norimatsu. (1995) Effects of single and concurrent intermittent administration of human parathyroid hormone and bisphosphonate cimadronate on bone mineral densities of femur in ovariectomized rats. Journal of Bone and Mineral Metabolism 13:1, 17-22
CrossRef213
John A. Eisman. (1995) Efficacy of treatment of osteoporotic fractures. The American Journal of Medicine 98:2, 17S-23S
CrossRef214
Ego Seeman. (1995) The dilemma of osteoporosis in men. The American Journal of Medicine 98:2, 76S-88S
CrossRef215
John A. Kants. (1995) Treatment of osteoporosis in elderly women. The American Journal of Medicine 98:2, 60S-66S
CrossRef216
R.W. Boyce, C.L. Paddock, J.R. Gleason, W.K. Sletsema, E.F. Eriksen. (1995) The effects of risedronate on canine cancellous bone remodeling: Three-dimensional kinetic reconstruction of the remodeling site. Journal of Bone and Mineral Research 10:2, 211-221
CrossRef217
Dennis M. Black. (1995) Why elderly women should be screened and treated to prevent osteoporosis. The American Journal of Medicine 98:2, 67S-75S
CrossRef218
Olof Johnell. (1995) Prevention of fractures in the elderly: A review. Acta Orthopaedica 66:1, 90-98
CrossRef219
D. Chappard, P. Minaire, C. Privat, E. Berard, J. Mendoza-Sarmiento, H. Tournebise, Mf Basle, M. Audran, A. Rebel, C. Picot, C. Gaud. (1995) Effects of tiludronate on bone loss in paraplegic patients. Journal of Bone and Mineral Research 10:1, 112-118
CrossRef220
P.-T. Cheng, C. Chan, K. Müller. (1995) Cyclical treatment of osteopenic ovariectomized adult rats with PTH(1-34) and pamidronate. Journal of Bone and Mineral Research 10:1, 119-126
CrossRef221
J.S. Thomsen, Li. Mosekilde, R.W. Boyce, E. Mosekilde. (1994) Stochastic simulation of vertebral trabecular bone remodeling. Bone 15:6, 655-666
CrossRef222
M. Rossini, D. Gatti, N. Zamberlan, V. Braga, R. Dorizzi, S. Adami. (1994) Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. Journal of Bone and Mineral Research 9:11, 1833-1837
CrossRef223
Gerard M. Hall, Maxine Daniels, David V. Doyle, Tim D. Spector. (1994) Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis & Rheumatism 37:10, 1499-1505
CrossRef224
A. J. CURLE, J. A. CANTRILL. (1994) Patient acceptability of cyclical etidronate and calcium therapy and symptomatic response to treatment. International Journal of Pharmacy Practice 3:1, 19-23
CrossRef225
P. J. Ryan, I. Fogelman. (1994) Clinical experience with etidronate in osteoporosis. Clinical Rheumatology 13:3, 455-458
CrossRef226
Andrea Crosignani, Pier Maria Battezzati, Walter Albisetti, Giuseppe Grandinetti, Luca Pietrogrande, Arianna Biffi, Massimo Zuin, Mauro Podda. (1994) Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis. Hepatology 20:3, 633-637
CrossRef227
S. M. Orme, M. Simpson, S. P. Stewart, B. Oldroyd, C. F. Westmacott, M. A. Smith, P. E. Belchetz. (1994) Comparison of changes in bone mineral in idiopathic and secondary osteoporosis following therapy with cyclical disodium etidronate and high dose calcium supplementation. Clinical Endocrinology 41:2, 245-250
CrossRef228
S.J. Skingle, A.J. Crisp. (1994) Increased bone density in patients on steroids with etidronate. The Lancet 344:8921, 543-544
CrossRef229
F. I. Tovey, M. L. Hall, P. J. Ell, M. Hobsley. (1994) Cyclical etidronate therapy and postgastrectomy osteoporosis. British Journal of Surgery 81:8, 1168-1169
CrossRef230
Michael J. Rogers, Donald J. Watts, R. Graham G. Russell, Xiaohui Ji, Xiaojuan Xiong, G. Michael Blackburn, Allan V. Bayless, Frank H. Ebetino. (1994) Inhibitory effects of bisphosphonates on growth of amoebae of the cellular slime mold dictyostelium discoideum. Journal of Bone and Mineral Research 9:7, 1029-1039
CrossRef231
M. A. Damario, J. A. Rock. (1994) Goserelin (Zoladex) versus danazol for endometriosis: the North American experience. BJOG: An International Journal of Obstetrics and Gynaecology 101:s10, 13-18
CrossRef232
Mary E. Melton, Michael L. Kochman. (1994) Reversal of severe osteoporosis with vitamin B12 and etidronate therapy in a patient with pernicious anemia. Metabolism 43:4, 468-469
CrossRef233
M. E. Lacy, J. A. Bevan, R. W. Boyce, A. D. Geddes. (1994) Antiresorptive drugs and trabecular bone turnover: Validation and testing of a computer model. Calcified Tissue International 54:3, 179-185
CrossRef234
D. Thiébaud, P. Burckhardt, J. Melchior, P. Eckert, A. F. Jacquet, P. Schnyder, C. Gobelet. (1994) Two years' effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the postmenopause. Osteoporosis International 4:2, 76-83
CrossRef235
B.L. Riggs, W.M. O'Fallon, A. Lane, S.F. Hodgson, H.W. Wahner, J. Muhs, E. Chao, L.J. Melton. (1994) Clinical trial of fluoride therapy in postmenopausal osteoporotic women: Extended observations and additional analysis. Journal of Bone and Mineral Research 9:2, 265-275
CrossRef236
Pei-Tak Cheng, Cary C. K. Chan, Klaus Müller. (1994) Sequential treatment of osteopenic ovariectomized rats with parathyroid hormone (1-34) fragment and pamidronate. Journal of Bone and Mineral Metabolism 12:S1, S121-S124
CrossRef237
Giovanni Rolla, Caterina Bucca, Luisa Brussino. (1994) Bisphosphonate-induced bronchoconstriction In aspirin-sensitive asthma. The Lancet 343:8894, 426-427
CrossRef238
H. Ancher Sørensen, J.-E. Bech Jensen, O. Helmer Sørensen. (1994) Measurement of regional bone mass in normals and in osteoporotics. Scandinavian Journal of Clinical & Laboratory Investigation 54:s219, 42-46
CrossRef239
ANNIE W.C. KUNG, F. NG. (1994) A Rat Model of Thyroid Hormone-Induced Bone Loss: Effect of Antiresorptive Agents on Regional Bone Density and Osteocalcin Gene Expression. Thyroid 4:1, 93-98
CrossRef240
Patrick Ammann, René Rizzoli, Joseph Caverzasio, Takashi Shigematsu, Daniel Slosman, Jean-Philippe Bonjour. (1993) Effects of the bisphosphonate tiludronate on bone resorption, calcium balance, and bone mineral density. Journal of Bone and Mineral Research 8:12, 1491-1498
CrossRef241
Susan M. Ott. (1993) Clinical effects of bisphosphonates in involutional osteoporosis. Journal of Bone and Mineral Research 8:S2, S597-S606
CrossRef242
Marie-Claude Monier-Faugere, Robert M. Friedler, Frieder Bauss, Hartmut H. Malluche. (1993) A new bisphosphonate, BM 21.0955, prevents bone loss associated with cessation of ovarian function in experimental dogs. Journal of Bone and Mineral Research 8:11, 1345-1355
CrossRef243
L. Hyldstrup, G. Flesch, S. A. Hauffe. (1993) Pharmacokinetic evaluation of pamidronate after oral administration: A study on dose proportionality, absolute bioavailability, and effect of repeated administration. Calcified Tissue International 53:5, 297-300
CrossRef244
Harry K. Genant, Chun Y. Wu, Cornelis van Kuijk, Michael C. Nevitt. (1993) Vertebral fracture assessment using a semiquantitative technique. Journal of Bone and Mineral Research 8:9, 1137-1148
CrossRef245
John A Kanis, Jean Aaron, Monique Benéton, Eugene McCloskey. (1993) Treatment of osteoporosis. Journal of Bone and Mineral Metabolism 11:1, S17-S24
CrossRef246
M. L. TYAN. (1993) Effect of promethazine on lumbar vertebral bone mass in postmenopausal women. Journal of Internal Medicine 234:2, 143-148
CrossRef247
Roger Smith. (1993) Molecular, cellular and metabolic mechanisms of osteoporosis. Reviews in Clinical Gerontology 3:02, 107
CrossRef248
H. Fleisch. (1993) New bisphosphonates in osteoporosis. Osteoporosis International 3:S2, 15-22
CrossRef249
S. Giannini, A. D'Angelo, L. Malvasi, R. Castrignano, T. Pati, R. Tronca, L. Liberto, M. Nobile, G. Crepaldi. (1993) Effects of one-year cyclical treatment with clodronate on postmenopausal bone loss. Bone 14:2, 137-141
CrossRef250
Peter P. Antich, Charles Y.C. Pak, Jerome Gonzales, Jon Anderson, Khashayar Sakhaee, Craig Rubin. (1993) Measurement of intrinsic bone quality in vivo by reflection ultrasound: Correction of impaired quality with slow-release sodium fluoride and calcium citrate. Journal of Bone and Mineral Research 8:3, 301-311
CrossRef251
G. R. Mundy. (1993) Visions for the future in osteoporosis research. Osteoporosis International 3:S2, 29-34
CrossRef252
David B. Burr. (1993) Remodeling and the repair of fatigue damage. Calcified Tissue International 53:S1, S75-S81
CrossRef253
Tommy Storm, Torben Steiniche, Gorm Thamsborg, Fleming Melsen. (1993) Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis. Journal of Bone and Mineral Research 8:2, 199-208
CrossRef254
O. Johnell, M. Stenbeck, M. Rosen, B. Gullberg, J.A. Kanis. (1993) Therapeutic strategies in the prevention of hip fracture with drugs affecting bone metabolism. Bone 14, 85-87
CrossRef255
Neveen A.T. Hamdy. (1993) Role of bisphosphonates in metabolic bone diseases. Trends in Endocrinology & Metabolism 4:1, 19-25
CrossRef256
Colin J. Dunn, David V. Doyle, Derek A. Willoughby. (1993) Investigation of the acute and chronic anti-inflammatory properties of diphosphonates using a broad spectrum of immune and non-immune inflammatory reactions. Drug Development Research 28:1, 47-55
CrossRef257
Gideon A. Rodan, Raffaella Balena. (1993) Bisphosphonates in the Treatment of Metabolic Bone Diseases. Annals of Medicine 25:4, 373-378
CrossRef258
D. A. Nelson, M. Kleerekoper, E. Peterson, A. M. Parfitt. (1993) Skin color and body size as risk factors for osteoporosis. Osteoporosis International 3:1, 18-23
CrossRef259
F. I. TOVEY, M. L. HALL, P. J. ELL, M. HOBSLEY. (1992) A review of postgastrectomy bone disease. Journal of Gastroenterology and Hepatology 7:6, 639-645
CrossRef260
B.C. Toolan, M. Shea, E.R. Myers, R.E. Borchers, J.G. Seedor, H. Quartuccio, G. Rodan, W.C. Hayes. (1992) Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats. Journal of Bone and Mineral Research 7:12, 1399-1406
CrossRef261
Li Ya Tang, Webster S.S. Jee, Hua Zhu Ke, Donald B. Kimmel. (1992) Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure. Journal of Bone and Mineral Research 7:9, 1093-1104
CrossRef262
Lawrence A. Fleming. (1992) Osteoporosis. Journal of General Internal Medicine 7:5, 554-562
CrossRef263
Wood, Alastair J.J., , Riggs, B. Lawrence, Melton, L. Joseph III, . (1992) The Prevention and Treatment of Osteoporosis. New England Journal of Medicine 327:9, 620-627
Full Text264
D.D. Thompson, J.G. Seedor, H. Quartuccio, H. Solomon, C. Fioravanti, J. Davidson, H. Klein, R. Jackson, J. Clair, D. Frankenfield, E. Brown, H.A. Simmons, G.A. Rodan. (1992) The bisphosphonate, alendronate, prevents bone loss in ovariectomized baboons. Journal of Bone and Mineral Research 7:8, 951-960
CrossRef265
Meryl S. Leboff, Ghada El-Hajj Fuleihan, Jennifer E. Angell, Susan Chung, Kate Curtis. (1992) Dual-energy X-ray absorptiometry of the forearm: Reproducibility and correlation with single-photon absorptiometry. Journal of Bone and Mineral Research 7:7, 841-846
CrossRef266
Gerald B. Kasting, Marion D. Francis. (1992) Retention of etidronate in human, dog, and rat. Journal of Bone and Mineral Research 7:5, 513-522
CrossRef267
R. P. HEANEY. (1992) Calcium in the prevention and treatment of osteoporosis. Journal of Internal Medicine 231:2, 169-180
CrossRef268
P. T. Daley-Yates, D. J. Dodwell, M. Pongchaidecha, R. E. Coleman, A. Howell. (1991) The clearance and bioavailability of pamidronate in patients with breast cancer and bone metastases. Calcified Tissue International 49:6, 433-435
CrossRef269
J.Ph. Bonjour, R. Rizzoli. (1991) Métabolisme phosphocalcique: présent et avenir du traitement par les bisphosphonates. La Revue de Médecine Interne 12:6, S362-S365
CrossRef270
Jennifer A. McDonald, Colin R. Dunstan, Pamela Dilworth, Kenneth Sherbon, A. G. Ross Sheil, Richard A. Evans, Geoffrey W. McCaughan. (1991) Bone loss after liver transplantation. Hepatology 14:4, 613-619
CrossRef271
R.C. Mühlbauer, F. Bauss, R. Schenk, M. Janner, E. Bosies, K. Strein, H. Fleisch. (1991) BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. Journal of Bone and Mineral Research 6:9, 1003-1011
CrossRef272
Marco Janner, Roman C. Mühlbauer, Herbert Fleisch. (1991) Sodium EDTA enhances intestinal absorption of two bisphosphonates. Calcified Tissue International 49:4, 280-283
CrossRef273
P. D. Miller, B. J. Neal, D. O. McIntyre, M. J. Yanover, M. S. Anger, L. Kowalski. (1991) Effect of cyclical therapy with phosphorus and etidronate on axial bone mineral density in postmenopausal osteoporotic women. Osteoporosis International 1:3, 171-176
CrossRef274
Desforges, Jane F., , Johnston, C. Conrad Jr., Slemenda, Charles W., Melton, L. Joseph III, . (1991) Clinical Use of Bone Densitometry. New England Journal of Medicine 324:16, 1105-1109
Full Text275
T.J. Wronski, C.-F. Yen, K.S. Scott. (1991) Estrogen and diphosphonate treatment provide long-term protection against osteopenia in ovariectomized rats. Journal of Bone and Mineral Research 6:4, 387-394
CrossRef276
JOHN A. EISMAN. (1991) OsteoPPPOROSIS - Prevention, Prevention and Prevention. Australian and New Zealand Journal of Medicine 21:2, 205-210
CrossRef277
Gregory R. Mundy. (1991) Is prolonged stimulation of bone growth a therapeutic possibility?. Molecular and Cellular Endocrinology 75:2, C19-C25
CrossRef278
D. T. Baran, Clare Kearns McCarthy, D. Leahey, R. Lew4. (1991) Broadband ultrasound attenuation of the calcaneus predicts lumbar and femoral neck density in Caucasian women: A preliminary study. Osteoporosis International 1:2, 110-113
CrossRef279
John D. Osterloh. (1991) Observations on the effect of parathyroid hormone on environmental blood lead concentrations in humans. Environmental Research 54:1, 8-16
CrossRef280
Robert P. Heaney. (1991) How do we know what we know? The randomized controlled trial revisited. Journal of Bone and Mineral Research 6:2, 103-105
CrossRef281
Ian Joffe, Solomon Epstein. (1991) Osteoporosis associated with rheumatoid arthritis: Pathogenesis and management. Seminars in Arthritis and Rheumatism 20:4, 256-272
CrossRef282
Harold M. Frost. (1991) A new direction for osteoporosis research: A review and proposal. Bone 12:6, 429-437
CrossRef283
M. Hümpel, P. Günzel, H. Biere, B. Junginger. (1991) ZK 90 695: A new antiarthritic drug with tissue targeting properties. Agents and Actions 32:1-2, 22-23
CrossRef284
C. Cooper, I. Fogelman, L. J. Melton. (1991) Bisphosphonates and vertebral fracture: An epidemiological perspective. Osteoporosis International 2:1, 1-4
CrossRef285
Hans Mallmin, Sverker Ljunghall, Karin Larsson, Erik Lindh. (1991) Short-term Effects of Pamidronate on Biochemical Markers of Bone Metabolism in Osteoporosis—a Placebo-controlled Dose-finding Study. Upsala Journal of Medical Sciences 96:3, 205-212
CrossRef286
A. Vesterby, H.J.G. Gundersen, F. Melsen, L. Mosekilde. (1991) Marrow space star volume in the iliac crest decreases in osteoporotic patients after continuous treatment with fluoride, calcium, and vitamin D2 for five years. Bone 12:1, 33-37
CrossRef287
T. Steiniche, C. Hasling, P. Charles, E.F. Eriksen, F. Melsen, L. Mosekilde. (1991) The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: A randomized study comparing intermittent treatment and an ADFR regime. Bone 12:3, 155-163
CrossRef288
J. E. COMPSTON. (1990) REVIEW OSTEOPOROSIS. Clinical Endocrinology 33:5, 653-682
CrossRef289
(1990) Etidronate for Postmenopausal Osteoporosis. New England Journal of Medicine 323:17, 1209-1210
Full Text290
(1990) Effect of Fluoride on Postmenopausal Osteoporosis. New England Journal of Medicine 323:6, 416-417
Full Text291
Riggs, B. Lawrence, . (1990) A New Option for Treating Osteoporosis. New England Journal of Medicine 323:2, 124-125
Full Text292
Watts, Nelson B., Harris, Steven T., Genant, Harry K., Wasnich, Richard D., Miller, Paul D., Jackson, Rebecca D., Licata, Angelo A., Ross, Philip, Woodson, Grattan C. III, Yanover, Melissa J., Mysiw, W.Jerry, Kohse, Larry, Rao, M. Bhaskar, Steiger, Peter, Richmond, Bradford, Chesnut, Charles H. III, . (1990) Intermittent Cyclical Etidronate Treatment of Postmenopausal Osteoporosis. New England Journal of Medicine 323:2, 73-79
Full Text293
(1990) New treatments for osteoporosis. The Lancet 335:8697, 1065-1066
CrossRef294
William A. Stini. (1990) “Osteoporosis”: Etiologies, prevention, and treatment. American Journal of Physical Anthropology 33:S11, 151-194
CrossRef
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