Original Article
Denosumab in Postmenopausal Women with Low Bone Mineral Density
N Engl J Med 2006; 354:821-831February 23, 2006
- Abstract
Background
Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action.
Methods
The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of –1.8 to –4.0 at the lumbar spine or –1.8 to –3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase.
Results
Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent.
Conclusions
In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.)
Media in This Article
Figure 1
A Comparison of Changes in Bone Mineral Density (BMD) and Markers of Bone Turnover with Denosumab (Three-Month Regimen), Alendronate, and Placebo.Figure 2
A Comparison of Changes in Bone Mineral Density (BMD) and Markers of Bone Turnover with Denosumab (Six-Month Regimen), Alendronate, and Placebo.Article Activity
- Article
Osteoporosis is a well-established risk factor for fracture.1 Despite treatment options that reduce the risk of fracture in patients with osteoporosis, few patients fully adhere to current therapies. A recent study reported one-year adherence rates of less than 25 percent for all osteoporosis therapies examined.2 This adherence rate is substantially lower than that for therapies for other asymptomatic conditions, such as hypertension (50 to 70 percent adherence).3 Thus, new treatment approaches that engender high adherence are needed.
Receptor activator of nuclear factor-κB ligand (RANKL), a protein expressed by osteoblastic stromal cells, binds to receptor activator of nuclear factor-κB (RANK) and is the primary mediator of osteoclast differentiation, activation, and survival.4-8 RANKL is responsible for osteoclast-mediated bone resorption in a broad range of conditions. Osteoprotegerin, a soluble RANKL decoy receptor that binds RANKL, is the key endogenous regulator of the RANKL–RANK pathway.9
Denosumab (formerly known as AMG 162, Amgen) is a fully human monoclonal antibody (IgG2) that binds to RANKL with high affinity and specificity and blocks the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerin. In a phase 1 dose-escalation study, a single subcutaneous injection of denosumab resulted in a dose-dependent decrease in bone resorption, as measured by changes in serum and urinary N-telopeptide, markers of osteoclastic bone resorption.10
This article reports on a phase 2 study evaluating the efficacy and safety of denosumab in postmenopausal women with low bone mineral density.
Methods
Study Design
This randomized, placebo-controlled, dose-ranging study included eight double-blind groups and one open-label treatment group. A total of 412 women from 29 study centers in the United States were randomly assigned to receive denosumab given subcutaneously either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label alendronate (at a dose of 70 mg) given orally once weekly, or placebo. The randomization was stratified according to center with permuted blocks of eight. Amgen prepared the randomization schedule before the study began. The denosumab solution contained denosumab (30 or 70 mg per milliliter) in 5 percent sorbitol, with 10 mM sodium acetate in water for injection (pH 5.2). All subjects took daily oral supplements containing elemental calcium (1 g) and vitamin D (400 IU). The primary end point was the percentage change in bone mineral density at the lumbar spine at 12 months. Percentage changes from baseline in bone mineral density at the total hip, femoral neck, total body (minus head), and distal third of the radius were also assessed, as were serum levels of C-telopeptide, the urinary N-telopeptide:creatinine ratio, and bone-specific alkaline phosphatase.
Institutional review boards at each study site approved the study protocol, and all subjects provided written informed consent. Amgen designed the study in collaboration with the investigators, conducted statistical analyses, and interpreted the data, which it holds. The investigators had unrestricted access to the primary data and were not limited by the sponsor in the writing of this article. The authors were responsible for writing the article and vouch for its accuracy and completeness; editing assistance was provided by Amgen.
Subjects
Postmenopausal women up to 80 years of age were eligible if they had a bone mineral density T score of –1.8 to –4.0 at the lumbar spine or –1.8 to –3.5 at either the femoral neck or total hip. An upper limit of –1.8 was selected to include subjects with both osteopenia and osteoporosis. Exclusion criteria included the use of bisphosphonates within the previous 12 months or fluoride within the previous 24 months; tibolone, parathyroid hormone or any derivative, systemic glucocorticoids (more than 5 mg of prednisone equivalent daily for more than 10 days), inhaled glucocorticoids (more than 2000 μg daily for more than 10 days), anabolic steroids or testosterone within 6 months; and estrogens, selective estrogen receptor modulators, calcitonin, or calcitriol within 3 months before enrollment. Exclusion criteria included hyperparathyroidism or hypoparathyroidism, hyperthyroidism or hypothyroidism, hypocalcemia, rheumatoid arthritis, Paget's disease of bone, osteomalacia, a creatinine clearance of less than 35 ml per minute (as estimated by the Cockroft–Gault equation),11 malabsorption syndrome, a recent long-bone fracture (within the previous six months), more than one grade 1 vertebral fracture, an osteoporosis-related fracture within the previous two years, or a case in which bone mineral density could not be accurately measured.
Study Procedures
Measurements of bone mineral density of the lumbar spine, total hip, and femoral neck were performed by dual-energy x-ray absorptiometry (GE Lunar or Hologic) at baseline and at 1, 3, 6, and 12 months and of the distal third of the radius and total body at baseline and at 6 and 12 months. Quality control and scan analysis were performed at Bio-Imaging Technologies in Newtown, Pennsylvania. Levels of serum C-telopeptide (CrossLaps, Nordic Bioscience) and urine N-telopeptide (Osteomark) in fasting samples were measured at baseline, at 3 days, and monthly through 12 months, with an additional measurement 3 days after the 6-month visit. Bone-specific alkaline phosphatase (Tandem-R Ostase, Hybritech, or Access Ostase, Beckman Coulter) and intact parathyroid hormone (Nichols) were assessed at baseline and at months 1, 3, 6, 9 (bone-specific alkaline phosphatase only), and 12.
Hematologic and chemical analyses and serum levels of denosumab and denosumab-binding antibodies were recorded at all study visits. Antibodies detected by a validated electrochemiluminescent immunoassay were screened for denosumab-neutralizing activity by a cell-based tartrate-resistant acid phosphatase bioassay. (A detailed description of the assays appears in the Supplementary Appendix, which is available with the full text of this article at www.nejm.org). Reports of adverse events were collected spontaneously and in response to nondirected questioning at each study visit.
Statistical Analysis
Summary statistical analyses of demographic and baseline characteristics were calculated for all groups. Percentage changes from baseline for measures of bone metabolism were calculated for all subjects with a baseline value and at least one value after baseline and compared across dose groups (intention-to-treat). The mean percentage changes from baseline in bone mineral density and markers of bone turnover were determined by analysis of covariance models, with treatment as the main effect and the location of the center and the baseline value of the end point as covariates. The assumption of normality was assessed with use of the Shapiro–Wilk test.12 If the assumptions were violated, a nonparametric method (van Elteren test)13 was used to corroborate the parametric results. For the primary assessment, pairwise comparisons between each group receiving denosumab and the placebo group were conducted for each efficacy measure, and the levels of significance were adjusted for multiple testing with the use of the Hochberg procedure.14 With 40 subjects per treatment group and an assumed 20 percent dropout rate, a sample size of 32 subjects per group was needed to provide 90 percent power to detect a placebo-adjusted mean difference of 3 percent at a significance level of 0.05. A common standard deviation of 3.6 percent for percentage change in bone mineral density at the lumbar spine was assumed. To facilitate dose selection for subsequent studies, exploratory comparisons between the groups receiving denosumab and the alendronate group were performed. However, these comparisons were not among the primary objectives of the study and were not prespecified in either the protocol or the statistical-analysis plan; nominal P values are thus reported. Comparisons among denosumab, alendronate, and placebo in safety analyses were likewise descriptive, with nominal P values.
Results
Subjects
Data were collected from May 2002 to April 2004. Overall, 412 subjects were enrolled and 369 (90 percent) completed 12 months of treatment. The primary reasons for early discontinuation in the denosumab, alendronate, and placebo groups were withdrawal of consent (8, 2, and 7 percent, respectively, of all randomized subjects) and adverse events (2 percent for denosumab and 2 percent for placebo, with no subjects in the alendronate group). The mean age of the study population, which was similar across groups, was 63 years (Table 1Table 1
Demographic and Baseline Characteristics of the Study Population of 412 Subjects.). In rounded numbers, investigators classified 85 percent of the subjects as white, 11 percent as Hispanic, and 3 percent as black. The mean baseline levels of bone mineral density and markers of bone turnover were similar across the groups.Efficacy
Bone Mineral Density
Figure 1Figure 1
A Comparison of Changes in Bone Mineral Density (BMD) and Markers of Bone Turnover with Denosumab (Three-Month Regimen), Alendronate, and Placebo. and Figure 2Figure 2A Comparison of Changes in Bone Mineral Density (BMD) and Markers of Bone Turnover with Denosumab (Six-Month Regimen), Alendronate, and Placebo. depict measures of bone mineral density and clinical laboratory results over time in the groups that received denosumab every three months and every six months. Denosumab treatment was associated with a mean increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent at 12 months, as compared with a decrease of 0.8 percent in the placebo group (P<0.001) (Figure 1A and Figure 2A, and Table 1 of the Supplementary Appendix). Bone mineral density at the total hip at 12 months increased by a mean of 1.9 to 3.6 percent in the denosumab groups, as compared with a decrease of 0.6 percent in the placebo group (P<0.001) (Figure 1B and Figure 2B, and Table 1 of the Supplementary Appendix). At one month, increases in bone mineral density were observed at the lumbar spine and total hip in the groups receiving denosumab (in the groups receiving 14 mg and 30 mg of drug every three months and 60 mg every six months), as compared with the group receiving placebo (P<0.05). At 12 months, the bone mineral density at the distal third of the radius increased by 0.4 to 1.3 percent in the subjects receiving denosumab, as compared with a mean loss of 2.0 percent in the placebo group (P<0.001) (Figure 1C and Figure 2C, and Table 1 of the Supplementary Appendix). At 12 months, the mean percentage change in total body bone mineral density was 0.6 to 2.8 percent in the denosumab groups, as compared with –0.2 percent in the placebo group (P<0.01, except for subjects receiving 14 mg of drug every six months) (Figure 1D and Figure 2D, and Table 1 of the Supplementary Appendix). The most effective dose of denosumab in the group receiving the drug every three months appeared to be 30 mg; for the subjects on the every-six-month regimen, 60 mg appeared optimal, since higher doses were not more effective, and a dose of 14 mg was less effective.Alendronate increased bone mineral density, as compared with placebo, at 12 months. In exploratory comparisons, the observed mean changes in bone mineral density were at least as great with denosumab as with alendronate. These changes appeared to be greater at the distal third of the radius and total hip with denosumab at doses of 30 mg every three months and 60 mg every six months (Table 1 of the Supplementary Appendix).
Markers of Bone Turnover
The denosumab groups showed decreases in levels of serum C-telopeptide, as compared with the placebo group (P<0.001), as early as three days, the first scheduled time point after baseline (Figure 1E and Figure 2E, and Table 2 of the Supplementary Appendix). The maximum mean percentage reduction in levels of serum C-telopeptide was 88 percent among the denosumab groups, as compared with 6 percent in the placebo group. The duration of the decrease was dose-dependent. Partial reversibility in levels of serum C-telopeptide was observed in subjects receiving 6-mg doses every three months and 14-mg doses every six months; the effect was more sustained in the subjects receiving 14-mg and 30-mg doses every three months and 60-mg, 100-mg, and 210-mg doses every six months. The results of tests of the urinary N-telopeptide:creatinine ratio were similar to those for serum C-telopeptide (Table 3 of the Supplementary Appendix). There was a one-month delay in the decrease in bone-specific alkaline phosphatase levels, with reductions relative to placebo thereafter in all subjects receiving denosumab (P<0.001) (Figure 1F and Figure 2F, and Table 4 of the Supplementary Appendix).
Alendronate also reduced markers of bone turnover, as compared with placebo, throughout follow-up. Levels of serum C-telopeptide and urinary N-telopeptide decreased more rapidly, and at least as effectively, in subjects who received denosumab as in subjects who received alendronate, according to measurements taken at day 3 through month 3. Greater reductions continued to be observed through 12 months among subjects receiving the highest denosumab doses (30 mg every 3 months and 100 mg or more every 6 months) (Tables 2 and 3 of the Supplementary Appendix). Changes in bone-specific alkaline phosphatase were similar between the groups receiving denosumab and alendronate (Table 4 of the Supplementary Appendix).
Biochemical Analysis
The mean albumin-adjusted serum levels of calcium in denosumab-treated subjects demonstrated early but small decreases from baseline, as compared with the placebo and alendronate groups (Figure 1G and Figure 2G). Dose dependency of these changes was not observed. The lowest mean serum level of calcium (2.32 mmol per liter [reference range, 2.10 to 2.58]) was observed three days after the administration of 30 mg of denosumab every three months. The mean serum levels of calcium at day 3 in the alendronate and placebo groups were 2.41 and 2.44 mmol per liter, respectively. Six subjects receiving denosumab (1.9 percent) had albumin-adjusted serum calcium levels that fell below the reference range. The lowest recorded value (1.95 mmol per liter) occurred at two months in a subject who received 14 mg of denosumab every six months. These decreased values neither persisted nor were symptomatic.
Concentrations of intact parathyroid hormone increased in the denosumab and alendronate groups, as compared with placebo (Figure 1H and Figure 2H). The maximum mean level of intact parathyroid hormone in any denosumab group was 10.5 pmol per liter (reference range, 1.1 to 6.9) at one month in the group that received 210 mg of denosumab every six months (5.7 pmol per liter at baseline). For comparison, the mean concentrations of intact parathyroid hormone at one month in the placebo and alendronate groups were 5.0 and 7.8 pmol per liter, respectively. The increased levels returned toward baseline levels over time. At 12 months, the mean concentrations of intact parathyroid hormone were 5.4 and 6.5 pmol per liter in the groups that received 60 mg and 210 mg of denosumab, respectively, every six months.
Adverse Events and Safety
No significant differences were observed between the profiles of adverse events in the denosumab groups and those in the placebo group and the alendronate group (P>0.05), with the exception of the incidence of dyspepsia, which appeared to be significantly greater in the alendronate group (Table 2Table 2
Adverse Events., which shows overall adverse events, and Table 3Table 3
Adverse Events Occurring in at Least 10 Percent of Subjects in Any Dose Group., which shows the incidence of adverse events occurring in at least 10 percent of subjects). Other than changes in levels of calcium and parathyroid hormone, as previously described, no clinically relevant changes in either blood chemistry or hematologic analysis were observed among treatment groups; there were no notable differences in group mean values, frequency of changes in toxicity grades, or individual trends over time.Two subjects who received denosumab at a dose of 100 mg every 6 months had detectable denosumab-binding antibodies, one at 1 month and the other at 12 months. The antibodies were not neutralizing on the basis of results from a bioassay. Changes in bone mineral density and markers of bone turnover in these two subjects were within the range of responses of other subjects in their treatment group. Neither of these subjects withdrew from the study, and antibodies were not detected in subsequent samples in either subject.
Discussion
The discovery of the RANKL–RANK pathway as the primary mediator of osteoclast differentiation, activation, and survival4,7-9 facilitated the design of molecules that specifically target this pathway for the treatment of osteoporosis. By mimicking the effect of endogenous osteoprotegerin, denosumab, a fully human monoclonal antibody to RANKL, inhibited bone resorption with a rapid onset of action and a sustained but reversible effect.10
The present study in 412 postmenopausal women with low bone mineral density demonstrated that denosumab, given subcutaneously at three-month or six-month intervals, can increase bone density, as compared with placebo, at sites rich in trabecular bone (lumbar spine) and cortical bone (femoral neck, total hip, distal third of the radius, and total body). Formal statistical analysis for dose dependency was not prespecified and was not conducted. However, on the basis of results of the statistical analysis comparing each denosumab group with placebo, descriptive statistics, and visual inspection of the data, it appeared that doses of 30 mg of denosumab every three months and 60 mg every six months provided maximal biologic effect at the minimum exposure dose.
The increased bone mineral density at the distal radius, which is composed mainly of cortical bone, differentiated the response to denosumab from the response to alendronate at this site. This effect of denosumab on cortical bone has been observed in preclinical studies, although the mechanism remains unclear to date.
The data indicate that denosumab has a rapid onset of action. The decrease in serum levels of C-telopeptide was near maximal three days after dosing. Differences between denosumab and alendronate in changes in markers of bone resorption appeared to be more pronounced than were differences in changes of bone-specific alkaline phosphatase or bone mineral density. The latter changes are possibly less dynamic than are markers of bone resorption.
Denosumab has a long plasma-circulating time after a single subcutaneous injection.10 In this study, decreased bone turnover was sustained for approximately six months or more after single denosumab doses of 60 mg or more. This effect was reversible, as indicated by a return of serum levels of C-telopeptide toward baseline by the end of the six-month period at lower doses.
Limitations of this study include the fact that alendronate treatment was not blinded, which may have confounded comparisons of tolerability. However, bone density scans were analyzed in a blinded fashion, and the effect of alendronate on bone mineral density (a 4.6 percent increase at the lumbar spine) was similar to results of a controlled study using the same dose.15 The small number of subjects in each group precluded conclusive assessment of the effect of therapy on the incidence of fracture.
In conclusion, denosumab that was administered subcutaneously at 3-month or 6-month intervals over a period of 12 months resulted in a sustained decrease in bone turnover and a rapid increase in bone mineral density. Increases in bone mineral density observed with denosumab appeared to be superior to those with placebo and similar to or greater than those with open-label alendronate (although this study was not designed to test equivalence). These results support the continued investigation of denosumab for use in the treatment and prevention of osteoporosis and other diseases associated with bone loss.
Supported by Amgen.
Dr. McClung reports having served as a consultant to Amgen, Eli Lilly, Merck, Novartis, NPS Pharmaceuticals, Procter & Gamble, Roche, Sanofi-Aventis, and Wyeth and having received grant support from Amgen, Eli Lilly, Merck, Novartis, Organon, Pfizer, Roche, and Sanofi-Aventis. Dr. Lewiecki reports having served as a consultant to Merck, Procter & Gamble, and Eli Lilly; having received lecture fees from Procter & Gamble; and having received grant support from Amgen. Dr. Cohen reports having served as a consultant to Amgen, Abbott, and Genentech; having equity interests in Merck and Pfizer; and having received lecture fees from Abbott, Genentech, and Amgen. Dr. Cohen is medical director of Radiant Research, Dallas, which receives grant support for clinical trials. Dr. Bolognese reports having received lecture fees from Eli Lilly, Roche, and Aventis. Dr. Woodson reports having received grant support from Amgen. Dr. Peacock reports having received consulting fees from Amgen. Dr. Miller reports having served as a consultant to Merck, Eli Lilly, Wyeth–Ayerst, Roche, Procter & Gamble, and Aventis; having received lecture fees from Eli Lilly, Procter & Gamble, Aventis, Roche, Amgen, Merck, and Novartis; and having received grant support from Merck, Procter & Gamble, Aventis, Eli Lilly, Roche, Novartis, and Amgen. Dr. Lederman reports having received lecture fees from Eli Lilly. Dr. Chesnut reports having received grant support from Amgen. Dr. Lain reports having equity interests in Merck and Pfizer. Dr. Kivitz reports having an equity interest in Amgen. Drs. Holloway, Zhang, Peterson, and Bekker report having equity interests in Amgen; at the time the study was conducted, they were employees of Amgen. No other potential conflict of interest relevant to this article was reported.
We are indebted to Clifton Chunn and Holly Brenza Zoog of Amgen for their assistance in the preparation of the manuscript.
Source Information
From Providence Portland Medical Center, Portland, Oreg. (M.R.M.); New Mexico Clinical Research and Osteoporosis Center, Albuquerque (E.M.L.); Radiant Research, Dallas (S.B.C.); Bethesda Health Research Center, Bethesda, Md. (M.A.B.); Atlanta Research Center, Decatur, Ga. (G.C.W.); OB-GYN Associates of Mid Florida, Leesburg, Fla. (A.H.M.); Indiana University School of Medicine, Indianapolis (M.P.); Colorado Center for Bone Research, Lakewood (P.D.M.); Radiant Research, Lake Worth, Fla. (S.N.L.); University of Washington Medical Center, Seattle (C.H.C.); Arthritis Associates and Osteoporosis Center of Colorado Springs, Colorado Springs, Colo. (D.L.); Altoona Center for Clinical Research, Duncansville, Pa. (A.J.K.); and Amgen, Thousand Oaks, Calif. (D.L.H., C.Z., M.C.P., P.J.B.).
Address reprint requests to Dr. McClung at the Oregon Osteoporosis Center, 5050 NE Hoyt St., Suite 651, Portland, OR 97213, or at mmcclung@orost.com.
Other members of the AMG 162 (Denosumab) Bone Loss Study Group are listed in the Appendix.
Appendix
In addition to the authors, other members of the AMG 162 Bone Loss Study Group were as follows: A. Jaffer, Allergy and Rheumatology, La Jolla, Calif.; M. Kipnes, Diabetes and Glandular Disease Clinic, San Antonio, Tex.; P. Leese, Quintiles Phase 1 Services, Lenexa, Kans.; M. Layton, South Puget Sound Clinical Research Center, Olympia, Wash.; M. Kohen, Coastal Medical Research, Port Orange, Fla.; N. Watts, University of Cincinnati Bone Health and Osteoporosis Center, Cincinnati; R. Weinstein, Diablo Clinical Research, Walnut Creek, Calif.; J. Schechtman, Sun Valley Arthritis Center, Glendale, Ariz.; P. Knibbe, Intermountain Research, Boise, Idaho; W. Koltun, Medical Center for Clinical Research, San Diego, Calif.; M. Block, Radiant Research, Phoenix, Ariz.; W. Larson, Radiant Research, Lakewood, Wash.; K. Aqua, Visions Clinical Research, Palm Springs, Fla.; D. Rider, Cal-West, San Francisco; E. Boling, Boling Clinical Trials, Rancho Cucamonga, Calif.; R. Emkey, Radiant Research, Wyomissing, Pa.; and J. Gresh, Renstar Medical Research, Ocala, Fla.
- References
References
1
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy
CrossRef | Web of Science2
McCombs JS ,Thiebaud P ,McLaughlin-Miley C ,Shi J . Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 2004;48:271-287
CrossRef | Web of Science | Medline3
Schroeder K ,Fahey T ,Ebrahim S . Interventions for improving adherence to treatment in patients with high blood pressure in ambulatory settings. Cochrane Database Syst Rev 2004;2:CD004804-CD004804
Medline4
Lacey DL ,Timms E ,Tan HL , et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-176
CrossRef | Web of Science | Medline5
Burgess TL ,Qian Y ,Kaufman S , et al. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol 1999;145:527-538
CrossRef | Web of Science | Medline6
Lacey DL ,Tan HL ,Lu J , et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol 2000;157:435-448
CrossRef | Web of Science | Medline7
Yasuda H ,Shima N ,Nakagawa N , et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998;95:3597-3602
CrossRef | Web of Science | Medline8
Hsu H ,Lacey DL ,Dunstan CR , et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A 1999;96:3540-3545
CrossRef | Web of Science | Medline9
Simonet WS ,Lacey DL ,Dunstan CR , et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309-319
CrossRef | Web of Science | Medline10
Bekker PJ ,Holloway DL ,Rasmussen AS , et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004;19:1059-1066
CrossRef | Web of Science | Medline11
Cockcroft D ,Gault M . Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41
CrossRef | Medline12
Shapiro SS ,Wilk MB . An analysis of variance test for normality (complete samples). Biometrika 1965;52:591-611
Web of Science13
van Elteren PH . On the combination of independent two-sample tests of Wilcoxon. Bull Int Stat Inst 1960;37:351-36114
Hochberg Y . A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988;75:800-802
CrossRef | Web of Science15
Schnitzer T ,Bone HG ,Crepaldi G , et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Aging (Milano) 2000;12:1-12
Medline
- Citing Articles (287)
Citing Articles
1
J.-J. Body, P. Bergmann, S. Boonen, J.-P. Devogelaer, E. Gielen, S. Goemaere, J.-M. Kaufman, S. Rozenberg, J.-Y. Reginster. (2012) Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications. Osteoporosis International 23:S1, 1-23
CrossRef2
T. Lin, C. Wang, X.-Z. Cai, X. Zhao, M.-M. Shi, Z.-M. Ying, F.-Z. Yuan, C. Guo, S.-G. Yan. (2012) Comparison of clinical efficacy and safety between denosumab and alendronate in postmenopausal women with osteoporosis: a meta-analysis. International Journal of Clinical Practiceno-no
CrossRef3
Pawel Szulc. (2012) The role of bone turnover markers in monitoring treatment in postmenopausal osteoporosis. Clinical Biochemistry
CrossRef4
Brian McClune, Navneet S. Majhail, Mary E.D. Flowers. (2012) Bone Loss and Avascular Necrosis of Bone After Hematopoietic Cell Transplantation. Seminars in Hematology 49:1, 59-65
CrossRef5
Jameela Banu, Erika Varela, Gabriel Fernandes. (2012) Alternative therapies for the prevention and treatment of osteoporosis. Nutrition Reviews 70:1, 22-40
CrossRef6
E. Michael Lewiecki, John P. Bilezikian, Lawrence G. Jankowski, Eugene V. McCloskey, Paul D. Miller, Sarah L. Morgan, Eric S. Orwoll, John T. Potts. (2012) Proceedings of the 2011 Santa Fe Bone Symposium. Journal of Clinical Densitometry 15:1, 1-20
CrossRef7
E M Lewiecki, J P Bilezikian. (2011) Denosumab for the Treatment of Osteoporosis and Cancer-Related Conditions. Clinical Pharmacology & Therapeutics
CrossRef8
E. Tsourdi, T. D. Rachner, M. Rauner, C. Hamann, L. C. Hofbauer. (2011) Denosumab for bone diseases: translating bone biology into targeted therapy. European Journal of Endocrinology 165:6, 833-840
CrossRef9
M.D. Cantley, D.P. Fairlie, P.M. Bartold, K.D. Rainsford, G.T. Le, A.J. Lucke, C.A. Holding, D.R. Haynes. (2011) Inhibitors of histone deacetylases in class I and class II suppress human osteoclasts in vitro. Journal of Cellular Physiology 226:12, 3233-3241
CrossRef10
Liviawati Sutjandra, Rachelle D. Rodriguez, Sameer Doshi, Mark Ma, Mark C. Peterson, Graham R. Jang, Andrew T. Chow, Juan José Pérez-Ruixo. (2011) Population Pharmacokinetic Meta-Analysis of Denosumab in Healthy Subjects and Postmenopausal Women with Osteopenia or Osteoporosis. Clinical Pharmacokinetics 50:12, 793-807
CrossRef11
Yuji Kumagai, Tomoko Hasunuma, Desmond Padhi. (2011) A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women. Bone 49:5, 1101-1107
CrossRef12
Marie-Paule Lecart, Jean-Yves Reginster. (2011) Current options for the management of postmenopausal osteoporosis. Expert Opinion on Pharmacotherapy 12:16, 2533-2552
CrossRef13
T. Mori, T. Miyamoto, H. Yoshida, M. Asakawa, M. Kawasumi, T. Kobayashi, H. Morioka, K. Chiba, Y. Toyama, A. Yoshimura. (2011) IL-1 and TNF -initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis. International Immunology 23:11, 701-712
CrossRef14
Lluís Pérez Edo, Alberto Alonso Ruiz, Daniel Roig Vilaseca, Alberto García Vadillo, Nuria Guañabens Gay, Pilar Peris, Antonio Torrijos Eslava, Chesús Beltrán Audera, Jordi Fiter Aresté, Luis Arboleya Rodríguez, Jenaro Graña Gil, Jordi Carbonell Abelló, Joan Miquel Nolla, Susana Holgado Pérez, Esteban Salas Heredia, Jaime Zubieta Tabernero, Javier Del Pino Montes, Josep Blanch i Rubió, Manuel Caamaño Freire, Manuel Rodríguez Pérez, Santos Castañeda, Dacia Cerdá, Carmen Gómez Vaquero, Javier Calvo Catalá, Manel Ciria, Estíbaliz Loza. (2011) Actualización 2011 del consenso Sociedad Española de Reumatología de osteoporosis. Reumatología Clínica 7:6, 357-379
CrossRef15
Mary Barna Bridgeman, Rolee Pathak. (2011) Denosumab for the Reduction of Bone Loss in Postmenopausal Osteoporosis: A Review. Clinical Therapeutics 33:11, 1547-1559
CrossRef16
Lluis Pérez Edo, Alberto Alonso Ruiz, Daniel Roig Vilaseca, Alberto García Vadillo, Nuria Guañabens Gay, Pilar Peris, Antonio Torrijos Eslava, Chesús Beltrán Audera, Jordi Fiter Aresté, Luis Arboleya Rodríguez, Jenaro Graña Gil, Jordi Carbonell Abelló, Joan Miquel Nolla, Susana Holgado Pérez, Esteban Salas Heredia, Jaime Zubieta Tabernero, Javier Del Pino Montes, Josep Blanch i. Rubió, Manuel Caamaño Freire, Manuel Rodríguez Pérez, Santos Castañeda, Dacia Cerdá, Carmen Gómez Vaquero, Javier Calvo Catalá, Manel Ciria, Estíbaliz Loza. (2011) 2011 Up-Date of the Consensus Statement of the Spanish Society of Rheumatology on Osteoporosis. Reumatolog ía Cl ínica (English Edition)
CrossRef17
M.-A. Quemerais-Durieu, V. Kerlan, O. Chabre. (2011) Innovations thérapeutiques dans l’ostéoporose (anticorps antisclérostine et denosumab). Annales d'Endocrinologie 72, S15-S22
CrossRef18
Camilla von Keyserlingk, Robert Hopkins, Athanasios Anastasilakis, Konstantinos Toulis, Ron Goeree, Jean-Eric Tarride, Feng Xie. (2011) Clinical Efficacy and Safety of Denosumab in Postmenopausal Women with Low Bone Mineral Density and Osteoporosis: A Meta-Analysis. Seminars in Arthritis and Rheumatism 41:2, 178-186
CrossRef19
Hou-Feng Zheng, Timothy D. Spector, J. Brent Richards. (2011) Insights into the genetics of osteoporosis from recent genome-wide association studies. Expert Reviews in Molecular Medicine 13,
CrossRef20
E. Seeman. (2011) Antiresorptive Agents Differ in Their Mode of Action and Morphological Effects. IBMS BoneKEy 8:10, 433-437
CrossRef21
, N. Freemantle, S. Satram-Hoang, E.-T. Tang, P. Kaur, D. Macarios, S. Siddhanti, J. Borenstein, D. L. Kendler. (2011) Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporosis International
CrossRef22
T. Nakamura, T. Matsumoto, T. Sugimoto, M. Shiraki. (2011) Dose–response study of denosumab on bone mineral density and bone turnover markers in Japanese postmenopausal women with osteoporosis. Osteoporosis International
CrossRef23
N. B. Watts, C. Roux, J. F. Modlin, J. P. Brown, A. Daniels, S. Jackson, S. Smith, D. J. Zack, L. Zhou, A. Grauer, S. Ferrari. (2011) Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association?. Osteoporosis International
CrossRef24
Emmet E. McGrath. (2011) OPG/RANKL/RANK Pathway as a Therapeutic Target in Cancer. Journal of Thoracic Oncology 6:9, 1468-1473
CrossRef25
Jordi Fiter Aresté. (2011) Presente y futuro de los anticuerpos monoclonales en el tratamiento de la osteoporosis. Reumatología Clínica 7, 8-12
CrossRef26
Ove Törring. (2011) Denosumab for treatment of osteoporosis in postmenopausal women. Clinical Investigation 1:9, 1329-1340
CrossRef27
Anke Heidewig Hautmann, Sharon Elad, Anita Lawitschka, Hildegard Greinix, Hartmut Bertz, Joerg Halter, Maura Faraci, Lorenz Christian Hofbauer, Stephanie Lee, Daniel Wolff, Ernst Holler. (2011) Metabolic bone diseases in patients after allogeneic hematopoietic stem cell transplantation: Report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease. Transplant International 24:9, 867-879
CrossRef28
Wolfgang Böcker, Tamara Radic, Veronika Schönitzer, Florian Haasters, Wolf Mutschler, Matthias Schieker. (2011) Molecular cloning and functional characterization of the porcine extracellular domain of Receptor Activator of NF-κB Ligand (sRANKL). Gene
CrossRef29
N. Guañabens, A. Monegal, A. Muxi, A. Martinez-Ferrer, R. Reyes, J. Caballería, L. Río, P. Peris, F. Pons, A. Parés. (2011) Patients with cirrhosis and ascites have false values of bone density. Osteoporosis International
CrossRef30
Kimberly Noonan, Ivan Borrello. (2011) The Immune Microenvironment of Myeloma. Cancer Microenvironment
CrossRef31
Cristina Alonso-Bouzon, Gustavo Duque. (2011) Osteoporosis senil: una actualización. Revista Española de Geriatría y Gerontología 46:4, 223-229
CrossRef32
Serge Cremers, Socrates Papapoulos. (2011) Pharmacology of bisphosphonates. Bone 49:1, 42-49
CrossRef33
Reiko Hanada, Toshikatsu Hanada, Verena Sigl, Daniel Schramek, Josef M. Penninger. (2011) RANKL/RANK—beyond bones. Journal of Molecular Medicine 89:7, 647-656
CrossRef34
Teh-Yuan Ho, Karen Santora, Joseph C. Chen, Amy-Lynn Frankshun, Carol A. Bagnell. (2011) Effects of relaxin and estrogens on bone remodeling markers, receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG), in rat adjuvant-induced arthritis. Bone 48:6, 1346-1353
CrossRef35
Loredana Cavalli, Maria Luisa Brandi. (2011) Age- and gender-related macro- and micro-architecture changes in bone structure and implications for treatment. International Journal of Clinical Rheumatology 6:3, 359-369
CrossRef36
, D. L. Kendler, M. R. McClung, N. Freemantle, M. Lillestol, A. H. Moffett, J. Borenstein, S. Satram-Hoang, Y.-C. Yang, P. Kaur, D. Macarios, S. Siddhanti. (2011) Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporosis International 22:6, 1725-1735
CrossRef37
Terri M Wensel, Maryam M Iranikhah, Teresa W Wilborn. (2011) Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women. Pharmacotherapy 31:5, 510-523
CrossRef38
James R. Edwards, Gregory R. Mundy. (2011) Advances in osteoclast biology: old findings and new insights from mouse models. Nature Reviews Rheumatology 7:4, 235-243
CrossRef39
Roland Baron, Serge Ferrari, R. Graham G. Russell. (2011) Denosumab and bisphosphonates: Different mechanisms of action and effects. Bone 48:4, 677-692
CrossRef40
Larry J. Suva, Charity Washam, Richard W. Nicholas, Robert J. Griffin. (2011) Bone metastasis: mechanisms and therapeutic opportunities. Nature Reviews Endocrinology 7:4, 208-218
CrossRef41
Tilman D Rachner, Sundeep Khosla, Lorenz C Hofbauer. (2011) Osteoporosis: now and the future. The Lancet 377:9773, 1276-1287
CrossRef42
Linda Brewer, David Williams, Alan Moore. (2011) Current and future treatment options in osteoporosis. European Journal of Clinical Pharmacology 67:4, 321-331
CrossRef43
Hector F DeLuca, Wendy Bedale, Neil Binkley, J Chris Gallagher, Michael Bolognese, Munro Peacock, John Aloia, Margaret Clagett-Dame, Lori Plum. (2011) The vitamin D analogue 2MD increases bone turnover but not BMD in postmenopausal women with osteopenia: Results of a 1-year phase 2 double-blind, placebo-controlled, randomized clinical trial. Journal of Bone and Mineral Research 26:3, 538-545
CrossRef44
Ioannis Charopoulos, Steve Orme, Peter V Giannoudis. (2011) The role and efficacy of denosumab in the treatment of osteoporosis: an update. Expert Opinion on Drug Safety 10:2, 205-217
CrossRef45
Jean-Baptiste Lattouf, Hicham Fadlallah, Fred Saad. (2011) Androgen Deprivation and Bone. Current Osteoporosis Reports 9:1, 20-24
CrossRef46
Ulrika Islander, Caroline Jochems, Marie K. Lagerquist, Helena Forsblad-d’Elia, Hans Carlsten. (2011) Estrogens in rheumatoid arthritis; the immune system and bone. Molecular and Cellular Endocrinology 335:1, 14-29
CrossRef47
Cesar E. Bogado, Maria Belen Zanchetta, Juan A. Boailchuk, Fabio E. Massari, Jose R. Zanchetta. (2011) Denosumab: What’s New?. Current Osteoporosis Reports 9:1, 12-19
CrossRef48
Richard Eastell, Claus Christiansen, Andreas Grauer, Stepan Kutilek, Cesar Libanati, Michael R McClung, Ian R Reid, Heinrich Resch, Ethel Siris, Daniel Uebelhart, Andrea Wang, Georges Weryha, Steve R Cummings. (2011) Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. Journal of Bone and Mineral Research 26:3, 530-537
CrossRef49
Pooneh Salari Sharif, Mohammad Abdollahi, Bagher Larijani. (2011) Current, new and future treatments of osteoporosis. Rheumatology International 31:3, 289-300
CrossRef50
Hassan Mansouritorghabeh, Zahra Rezaieyazdi. (2011) Bleeding disorders and reduced bone density. Rheumatology International 31:3, 283-287
CrossRef51
Barbara C. Silva, John P. Bilezikian. (2011) New Approaches to the Treatment of Osteoporosis. Annual Review of Medicine 62:1, 307-322
CrossRef52
David RP Guay. (2011) Denosumab: a novel biological therapy for osteoporosis. Aging Health 7:1, 13-43
CrossRef53
, S. Vasikaran, R. Eastell, O. Bruyère, A. J. Foldes, P. Garnero, A. Griesmacher, M. McClung, H. A. Morris, S. Silverman, T. Trenti, D. A. Wahl, C. Cooper, J. A. Kanis. (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporosis International 22:2, 391-420
CrossRef54
S. Ferrari-Lacraz, S. Ferrari. (2011) Do RANKL inhibitors (denosumab) affect inflammation and immunity?. Osteoporosis International 22:2, 435-446
CrossRef55
Wang-Hee Lee, Meryl E. Wastney, George S. Jackson, Berdine R. Martin, Connie M. Weaver. (2011) Interpretation of 41Ca data using compartmental modeling in post-menopausal women. Analytical and Bioanalytical Chemistry 399:4, 1613-1622
CrossRef56
Masanobu Kawai, Ulrike I. Mödder, Sundeep Khosla, Clifford J. Rosen. (2011) Emerging therapeutic opportunities for skeletal restoration. Nature Reviews Drug Discovery 10:2, 141-156
CrossRef57
E. Michael Lewiecki, John P. Bilezikian, Sundeep Khosla, Robert Marcus, Michael R. McClung, Paul D. Miller, Nelson B. Watts, Michael Maricic. (2011) Osteoporosis Update From the 2010 Santa Fe Bone Symposium. Journal of Clinical Densitometry 14:1, 1-21
CrossRef58
Unni Syversen, Johan Halse, Jürgen Geisler, Erik Eriksen. (2011) Denosumab for behandling av postmenopausal osteoporose. Tidsskrift for Den norske legeforening 131:19, 1893-1896
CrossRef59
Yoshiya Tanaka, Nobuyuki Miyasaka. (2011) Recent progress in small molecular products for the treatment of joint and bone diseases: an over view. Inflammation and Regeneration 31:4, 341-343
CrossRef60
Morten A Karsdal, Thasia Woodworth, Kim Henriksen, Walter P Maksymowych, Harry Genant, Philippe Vergnaud, Claus Christiansen, Tanja Schubert, Per Qvist, Georg Schett, Adam Platt, Anne-Christine Bay-Jensen. (2011) Biochemical markers of ongoing joint damage in rheumatoid arthritis - current and future applications, limitations and opportunities. Arthritis Research & Therapy 13:2, 215
CrossRef61
Marit D. Moen, Susan J. Keam. (2011) Denosumab. Drugs & Aging 28:1, 63-82
CrossRef62
Alicia K. Morgans, Matthew R. Smith. (2011) RANKL-Targeted Therapies: The Next Frontier in the Treatment of Male Osteoporosis. Journal of Osteoporosis 2011, 1-6
CrossRef63
Luis Pérez Edo. (2011) La inhibición del RANKL en el tratamiento de la osteoporosis: denosumab. Seminarios de la Fundación Española de Reumatología 12:1, 27-30
CrossRef64
J. Christopher Gallagher, Jeffrey P. Levine. (2011) Preventing osteoporosis in symptomatic postmenopausal women. Menopause 18:1, 109-118
CrossRef65
MR McClung, S Boonen, O Törring, C Roux, R Rizzoli, HG Bone, C-L Benhamou, WF Lems, S Minisola, J Halse, HC Hoeck, R Eastell, A Wang, S Siddhanti, SR Cummings. (2011) Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. Journal of Bone and Mineral Researchn/a-n/a
CrossRef66
Reiko Hanada, Toshikatsu Hanada, Josef M. Penninger. (2010) Physiology and pathophysiology of the RANKL/RANK system. Biological Chemistry 391:12, 1365-1370
CrossRef67
, Hans Peter Dimai, Peter Pietschmann, Heinrich Resch, Elisabeth Preisinger, Astrid Fahrleitner-Pammer, Harald Dobnig, Klaus Klaushofer. (2010) Österreichischer Leitfaden zur medikamentösen Therapie der postmenopausalen Osteoporose: Addendum 2010. Wiener Medizinische Wochenschrift 160:21-22, 586-589
CrossRef68
Mohammad Tabrizi, Cherryl Funelas, Hamza Suria. (2010) Application of Quantitative Pharmacology in Development of Therapeutic Monoclonal Antibodies. The AAPS Journal 12:4, 592-601
CrossRef69
Emese Kiss, Zénó Kuluncsics, Zoltán Kiss, Gyula Poór. (2010) Biotechnológiai fejlesztések a monoklonálisantitest-terápiában: a RANK-ligand-gátló antitest. Orvosi Hetilap 151:52, 2137-2144
CrossRef70
Ego Seeman. (2010) Bone morphology in response to alendronate as seen by high-resolution computed tomography: Through a glass darkly. Journal of Bone and Mineral Research 25:12, 2553-2557
CrossRef71
Victoria J. Muir, Lesley J. Scott. (2010) Denosumab. BioDrugs 24:6, 379-386
CrossRef72
Ighovwerha Ofotokun, M Neale Weitzmann. (2010) HIV-1 infection and antiretroviral therapies: risk factors for osteoporosis and bone fracture. Current Opinion in Endocrinology, Diabetes and Obesity 17:6, 523-529
CrossRef73
Steven L. Teitelbaum. (2010) Stem Cells and Osteoporosis Therapy. Cell Stem Cell 7:5, 553-554
CrossRef74
P. D. Miller, R. J. Derman. (2010) What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?. Osteoporosis International 21:11, 1793-1802
CrossRef75
Masanori Koide, Saya Kinugawa, Naoyuki Takahashi, Nobuyuki Udagawa. (2010) Osteoclastic bone resorption induced by innate immune responses. Periodontology 2000 54:1, 235-246
CrossRef76
Eva Ringdal Pedersen, Thor Ueland, Reinhard Seifert, Pål Aukrust, Hall Schartum-Hansen, Marta Ebbing, Øyvind Bleie, Jannicke Igland, Gard Svingen, Jan Erik Nordrehaug, Ottar Nygård. (2010) Serum osteoprotegerin levels and long-term prognosis in patients with stable angina pectoris. Atherosclerosis 212:2, 644-649
CrossRef77
J.-J. Body, P. Bergmann, S. Boonen, Y. Boutsen, J.-P. Devogelaer, S. Goemaere, J.-M. Kaufman, S. Rozenberg, J.-Y. Reginster. (2010) Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club. Osteoporosis International 21:10, 1657-1680
CrossRef78
Dennis J. Cada, Terri L. Levien, Danial E. Baker. (2010) Formulary Drug Reviews - Denosumab. Hospital Pharmacy 45:10, 785-793
CrossRef79
Ian R Reid, Paul D Miller, Jacques P Brown, David L Kendler, Astrid Fahrleitner-Pammer, Ivo Valter, Katre Maasalu, Michael A Bolognese, Grattan Woodson, Henry Bone, Beiying Ding, Rachel B Wagman, Javier San Martin, Michael S Ominsky, David W Dempster. (2010) Effects of denosumab on bone histomorphometry: The FREEDOM and STAND studies. Journal of Bone and Mineral Research 25:10, 2256-2265
CrossRef80
Dan Feng, Dong Mei Wei, Juan Zhou, Xu Han, Fuxia Chen, Fang Fang, Fang Fang. 2010. Denosumab for osteoporosis in nonmetastatic prostate cancer patients receiving androgen-deprivation therapy. .
CrossRef81
Ernesto Canalis. (2010) New Treatment Modalities in Osteoporosis. Endocrine Practice 16:5, 855-863
CrossRef82
Eduardo Maldonado-Gonzales, Peter Pietschmann. (2010) An antibody against RANKL for the treatment of osteoporosis, inflammatory and malignant bone diseases. Wiener Medizinische Wochenschrift 160:17-18, 458-463
CrossRef83
Christian Beyer, Georg Schett. (2010) Novel targets in bone and cartilage. Best Practice & Research Clinical Rheumatology 24:4, 489-496
CrossRef84
Jie Zhang, David T. Redden, Gerald McGwin, Leigh F. Callahan, Edwin A. Smith, Graciela S. Alarcón, Larry W. Moreland, Désirée M. van der Heijde, Elizabeth E. Brown, Donna K. Arnett, Ted R. Mikuls, S. Louis Bridges. (2010) Generalized bone loss as a predictor of three-year radiographic damage in African American patients with recent-onset rheumatoid arthritis. Arthritis & Rheumatism 62:8, 2219-2226
CrossRef85
Ego Seeman, Pierre D Delmas, David A Hanley, Deborah Sellmeyer, Angela M Cheung, Elizabeth Shane, Ann Kearns, Thierry Thomas, Steven K Boyd, Stephanie Boutroy, Cesar Bogado, Sharmila Majumdar, Michelle Fan, Cesar Libanati, Jose Zanchetta. (2010) Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate. Journal of Bone and Mineral Research 25:8, 1886-1894
CrossRef86
T. Ishii, J. Kikuta, A. Kubo, M. Ishii. (2010) Control of Osteoclast Precursor Migration: A Novel Point of Control for Osteoclastogenesis and Bone Homeostasis. IBMS BoneKEy 7:8, 279-286
CrossRef87
Sheryl Martin-Moe, Tim Osslund, Y. John Wang, Tahir Mahmood, Rohini Deshpande, Susan Hershenson. 2010. The Structure of Biological Therapeutics. , 1-40.
CrossRef88
George W. Sledge, Aparna C. Jotwani, Lida Mina. (2010) Targeted Therapies in Early-Stage Breast Cancer: Achievements and Promises. Surgical Oncology Clinics of North America 19:3, 669-679
CrossRef89
KS Brar. (2010) Prevalent and emerging therapies for osteoporosis. Medical Journal Armed Forces India 66:3, 249-254
CrossRef90
H.K. Genant, K. Engelke, D.A. Hanley, J.P. Brown, M. Omizo, H.G. Bone, A.J. Kivitz, T. Fuerst, H. Wang, M. Austin, C. Libanati. (2010) Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 47:1, 131-139
CrossRef91
L. Jørgensen, A. Vik, N. Emaus, J. Brox, J.-B. Hansen, E. Mathiesen, P. Vestergaard. (2010) Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-κB ligand: the Tromsø Study. Osteoporosis International 21:6, 931-938
CrossRef92
E. Michael Lewiecki. (2010) Treatment of osteoporosis with denosumab. Maturitas 66:2, 182-186
CrossRef93
D. L. Kendler, L. Bessette, C. D. Hill, D. T. Gold, R. Horne, S. F. Varon, J. Borenstein, H. Wang, H.-S. Man, R. B. Wagman, S. Siddhanti, D. Macarios, H. G. Bone. (2010) Preference and satisfaction with a 6-month subcutaneous injection versus a weekly tablet for treatment of low bone mass. Osteoporosis International 21:5, 837-846
CrossRef94
P. Musette, M. L. Brandi, P. Cacoub, J. M. Kaufman, R. Rizzoli, J.-Y. Reginster. (2010) Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity. Osteoporosis International 21:5, 723-732
CrossRef95
James R. Berenson, Kenneth C. Anderson, Robert A. Audell, Ralph V. Boccia, Morton Coleman, Meletios A. Dimopoulos, Matthew T. Drake, Rafael Fonseca, Jean-Luc Harousseau, Douglas Joshua, Sagar Lonial, Ruben Niesvizky, Antonio Palumbo, G. David Roodman, Jesus F. San-Miguel, Seema Singhal, Donna M. Weber, Maurizio Zangari, Eric Wirtschafter, Ori Yellin, Robert A. Kyle. (2010) Monoclonal gammopathy of undetermined significance: a consensus statement. British Journal of Haematologyno-no
CrossRef96
Tara L. Aghaloo, Alan L. Felsenfeld, Sotirios Tetradis. (2010) Osteonecrosis of the Jaw in a Patient on Denosumab. Journal of Oral and Maxillofacial Surgery 68:5, 959-963
CrossRef97
Sougata Karmakar, Jonathan Kay, Ellen M. Gravallese. (2010) Bone Damage in Rheumatoid Arthritis: Mechanistic Insights and Approaches to Prevention. Rheumatic Disease Clinics of North America 36:2, 385-404
CrossRef98
Jean-Baptiste Lattouf, Fred Saad. (2010) Bone complications of androgen deprivation therapy: screening, prevention, and treatment. Current Opinion in Urology 20:3, 247-252
CrossRef99
Sophie Roux. (2010) New treatment targets in osteoporosis. Joint Bone Spine 77:3, 222-228
CrossRef100
John T. Sharp, Wayne Tsuji, Peter Ory, Cristina Harper-Barek, Huei Wang, Richard Newmark. (2010) Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care & Research 62:4, 537-544
CrossRef101
Solenne Pelletier, Roland Chapurlat. (2010) Optimizing bone health in chronic kidney disease. Maturitas 65:4, 325-333
CrossRef102
K.H. Taylor, L.S. Middlefell, K.D. Mizen. (2010) Osteonecrosis of the jaws induced by anti-RANK ligand therapy. British Journal of Oral and Maxillofacial Surgery 48:3, 221-223
CrossRef103
Serge Rozenberg. (2010) New therapeutic targets and agents for osteoporosis. Maturitas 65:4, 299-300
CrossRef104
Nishma Manek. (2010) Missed opportunities for osteoporosis management in older patients: a literature review. Primary Health Care Research & Development 11:02, 155
CrossRef105
Aymen I. Idris, Euphemie Landao-Bassonga, Stuart H. Ralston. (2010) The TRPV1 ion channel antagonist capsazepine inhibits osteoclast and osteoblast differentiation in vitro and ovariectomy induced bone loss in vivo. Bone 46:4, 1089-1099
CrossRef106
P J Saylor, M R Smith. (2010) Bone health and prostate cancer. Prostate Cancer and Prostatic Diseases 13:1, 20-27
CrossRef107
Mark S Nanes. (2010) Preventing metastases to bone: Denosumab or bisphosphonates?. Journal of Bone and Mineral Research 25:3, 437-439
CrossRef108
Chandrasekar Palaniswamy, Dhana Rekha Selvaraj, Varuni Rao, Umesh Patel. (2010) Newer Therapies for Osteoporosis. American Journal of Therapeutics 17:2, 197-200
CrossRef109
Teun M. Post, Serge C.L.M. Cremers, Thomas Kerbusch, Meindert Danhof. (2010) Bone Physiology, Disease and Treatment. Clinical Pharmacokinetics 49:2, 89-118
CrossRef110
&NA;. (2010) Management of osteoporosis in postmenopausal women. Menopause 17:1, 25-54
CrossRef111
David L Kendler, Christian Roux, Claude Laurent Benhamou, Jacques P Brown, Michael Lillestol, Suresh Siddhanti, Hoi-Shen Man, Javier San Martin, Henry G Bone. (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. Journal of Bone and Mineral Research 25:1, 72-81
CrossRef112
E. Michael Lewiecki, John P. Bilezikian, Andrew J. Laster, Paul D. Miller, Robert R. Recker, R. Graham G. Russell, Michael P. Whyte. (2010) 2009 Santa Fe Bone Symposium. Journal of Clinical Densitometry 13:1, 1-9
CrossRef113
Mark C. Peterson, Matthew M. Riggs. (2010) A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Bone 46:1, 49-63
CrossRef114
Kendall F. Moseley, Suzanne M. Jan de Beur. 2010. Osteoporosis in Men and Women. , 716-736.
CrossRef115
M TABBAL. 2010. Future TherapiesStrontium, SERMs, SARMs and New Therapies on the Horizon. , 713-732.
CrossRef116
Peter R. Ebeling. (2009) Metabolic bone diseases: Translational research—preventing fractures with denosumab. Nature Reviews Rheumatology 5:12, 660-661
CrossRef117
Kofi A. Mensah, Jie Li, Edward M. Schwarz. (2009) The emerging field of osteoimmunology. Immunologic Research 45:2-3, 100-113
CrossRef118
Hiroshi Takayanagi. (2009) Osteoimmunology and the effects of the immune system on bone. Nature Reviews Rheumatology 5:12, 667-676
CrossRef119
Piet Geusens. (2009) Strategies for treatment to prevent fragility fractures in postmenopausal women. Best Practice & Research Clinical Rheumatology 23:6, 727-740
CrossRef120
Apostolos I Gogakos, Moira S Cheung, JH Duncan Bassett, Graham R Williams. (2009) Bone signaling pathways and treatment of osteoporosis. Expert Review of Endocrinology & Metabolism 4:6, 639-650
CrossRef121
Philip J. Saylor, Nancy L. Keating, Matthew R. Smith. (2009) Prostate Cancer Survivorship: Prevention and Treatment of the Adverse Effects of Androgen Deprivation Therapy. Journal of General Internal Medicine 24:S2, 389-394
CrossRef122
Riches, Philip L., McRorie, Euan, Fraser, William D., Determann, Catherine, Hof, Rob van't, Ralston, Stuart H., . (2009) Osteoporosis Associated with Neutralizing Autoantibodies against Osteoprotegerin. New England Journal of Medicine 361:15, 1459-1465
Full Text123
A. Leibbrandt, J. M. Penninger. (2009) ESCI award lecture: from a little mouse to rationale medicine for bone loss. European Journal of Clinical Investigation 39:10, 842-850
CrossRef124
George Hajishengallis. (2009) Toll gates to periodontal host modulation and vaccine therapy. Periodontology 2000 51:1, 181-207
CrossRef125
E. Michael Lewiecki. (2009) Current and Emerging Pharmacologic Therapies for the Management of Postmenopausal Osteoporosis. Journal of Women's Health 18:10, 1615-1626
CrossRef126
Melissa D Cantley, Malcolm D Smith, David R Haynes. (2009) Pathogenic bone loss in rheumatoid arthritis: mechanisms and therapeutic approaches. International Journal of Clinical Rheumatology 4:5, 561-582
CrossRef127
Kurt Miller, Arnulf Stenzl, Bertrand Tombal. (2009) Advances in the Therapy of Prostate Cancer–Induced Bone Disease: Current Insights and Future Perspectives on the RANK/RANKL Pathways. European Urology Supplements 8:9, 747-752
CrossRef128
Bart L. Clarke. (2009) New and emerging treatments for osteoporosis. Clinical Endocrinology 71:3, 309-321
CrossRef129
Veerle Persy, Patrick D’Haese. (2009) Vascular calcification and bone disease: the calcification paradox. Trends in Molecular Medicine 15:9, 405-416
CrossRef130
Tomoki Nakashima, Hiroshi Takayanagi. (2009) Osteoimmunology: Crosstalk Between the Immune and Bone Systems. Journal of Clinical Immunology 29:5, 555-567
CrossRef131
Juliet Compston. (2009) Clinical and therapeutic aspects of osteoporosis. European Journal of Radiology 71:3, 388-391
CrossRef132
Tomoki Nakashima, Hiroshi Takayanagi. (2009) Osteoclasts and the immune system. Journal of Bone and Mineral Metabolism 27:5, 519-529
CrossRef133
Georg Schett, Marina Stolina, Denise Dwyer, Debra Zack, Stefan Uderhardt, Gerhard Krönke, Paul Kostenuik, Ulrich Feige. (2009) Tumor necrosis factor α and RANKL blockade cannot halt bony spur formation in experimental inflammatory arthritis. Arthritis & Rheumatism 60:9, 2644-2654
CrossRef134
Smith, Matthew R., Egerdie, Blair, Toriz, Narciso Hernández, Feldman, Robert, Tammela, Teuvo L.J., Saad, Fred, Heracek, Jiri, Szwedowski, Maciej, Ke, Chunlei, Kupic, Amy, Leder, Benjamin Z., Goessl, Carsten, . (2009) Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer. New England Journal of Medicine 361:8, 745-755
Full Text135
Khosla, Sundeep, . (2009) Increasing Options for the Treatment of Osteoporosis. New England Journal of Medicine 361:8, 818-820
Full Text136
Cummings, Steven R., Martin, Javier San, McClung, Michael R., Siris, Ethel S., Eastell, Richard, Reid, Ian R., Delmas, Pierre, Zoog, Holly B., Austin, Matt, Wang, Andrea, Kutilek, Stepan, Adami, Silvano, Zanchetta, Jose, Libanati, Cesar, Siddhanti, Suresh, Christiansen, Claus, . (2009) Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. New England Journal of Medicine 361:8, 756-765
Full Text137
Susann Helas, Claudia Goettsch, Michael Schoppet, Ute Zeitz, Ute Hempel, Henning Morawietz, Paul J. Kostenuik, Reinhold G. Erben, Lorenz C. Hofbauer. (2009) Inhibition of Receptor Activator of NF-κB Ligand by Denosumab Attenuates Vascular Calcium Deposition in Mice. The American Journal of Pathology 175:2, 473-478
CrossRef138
Sanjeev Kakar, David Little, Thomas A Einhorn. (2009) Can We Improve Fixation and Outcomes in the Treatment of Femoral Neck Fractures? The Use of Pharmaceuticals. Journal of Orthopaedic Trauma 23:6, 413-421
CrossRef139
E Michael Lewiecki. (2009) Denosumab update. Current Opinion in Rheumatology 21:4, 369-373
CrossRef140
Jacques P. Brown, Caroline Albert, Bassam A. Nassar, Jonathan D. Adachi, David Cole, K. Shawn Davison, Kent C. Dooley, Andrew Don-Wauchope, Pierre Douville, David A. Hanley, Sophie A. Jamal, Robert Josse, Stephanie Kaiser, John Krahn, Richard Krause, Richard Kremer, Raymond Lepage, Elaine Letendre, Suzanne Morin, Daylily S. Ooi, Alexandra Papaioaonnou, Louis-Georges Ste-Marie. (2009) Bone turnover markers in the management of postmenopausal osteoporosis. Clinical Biochemistry 42:10-11, 929-942
CrossRef141
E. Michael Lewiecki. (2009) Denosumab for joints and bones. Current Rheumatology Reports 11:3, 196-201
CrossRef142
Atul F. Kamath. (2009) Current Controversies in Bisphosphonate Therapy. Orthopedics 32:7, 473-475
CrossRef143
Marco Borderi, Davide Gibellini, Fabio Vescini, Elisa De Crignis, Laura Cimatti, Carlo Biagetti, Livia Tampellini, Maria C Re. (2009) Metabolic bone disease in HIV infection. AIDS 23:11, 1297-1310
CrossRef144
Daniel H. Solomon, Joel S. Finkelstein, Nancy Shadick, Meryl S. LeBoff, Carl S. Winalski, Margaret Stedman, Roberta Glass, M. Alan Brookhart, Michael E. Weinblatt, Ellen M. Gravallese. (2009) The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritis. Arthritis & Rheumatism 60:6, 1624-1631
CrossRef145
Kim Henriksen, Anita V. Neutzsky-Wulff, Lynda F. Bonewald, Morten A. Karsdal. (2009) Local communication on and within bone controls bone remodeling. Bone 44:6, 1026-1033
CrossRef146
M.A. Karsdal, K. Henriksen, D.J. Leeming, P. Mitchell, K. Duffin, N. Barascuk, L. Klickstein, P. Aggarwal, O. Nemirovskiy, I. Byrjalsen, P. Qvist, A.C. Bay-Jensen, E.B. Dam, S.H. Madsen, C. Christiansen. (2009) Biochemical markers and the FDA Critical Path: How biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers 14:3, 181-202
CrossRef147
LS Holliday, DA Ostrov, TJ Wronski, C Dolce. (2009) Osteoclast polarization and orthodontic tooth movement. Orthodontics & Craniofacial Research 12:2, 105-112
CrossRef148
Lorenz C. Hofbauer, Ute Zeitz, Michael Schoppet, Monika Skalicky, Christiane Schüler, Marina Stolina, Paul J. Kostenuik, Reinhold G. Erben. (2009) Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis & Rheumatism 60:5, 1427-1437
CrossRef149
Nikolaus B Binder, Birgit Niederreiter, Oskar Hoffmann, Richard Stange, Thomas Pap, Thomas M Stulnig, Matthias Mack, Reinhold G Erben, Josef S Smolen, Kurt Redlich. (2009) Estrogen-dependent and C-C chemokine receptor-2–dependent pathways determine osteoclast behavior in osteoporosis. Nature Medicine 15:4, 417-424
CrossRef150
G. GERSTNER, M. L. DAMIANO, A. TOM, C. WORMAN, W. SCHULTZ, M. RECHT, A. T. STOPECK. (2009) Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia. Haemophilia 15:2, 559-565
CrossRef151
Robert W. Lash, Jane M. Nicholson, Lourdes Velez, R. Van Harrison, Jane McCort. (2009) Diagnosis and Management of Osteoporosis. Primary Care: Clinics in Office Practice 36:1, 181-198
CrossRef152
H. L. Wright, H. S. McCarthy, J. Middleton, M. J. Marshall. (2009) RANK, RANKL and osteoprotegerin in bone biology and disease. Current Reviews in Musculoskeletal Medicine 2:1, 56-64
CrossRef153
Tejas V. Patel, Ajay K. Singh. (2009) Kidney Disease Outcomes Quality Initiative Guidelines for Bone and Mineral Metabolism: Emerging Questions. Seminars in Nephrology 29:2, 105-112
CrossRef154
Paul D. Miller. (2009) Denosumab: Anti-RANKL antibody. Current Osteoporosis Reports 7:1, 18-22
CrossRef155
Gary T. Jennings, Martin F. Bachmann. (2009) Immunodrugs: Therapeutic VLP-Based Vaccines for Chronic Diseases. Annual Review of Pharmacology and Toxicology 49:1, 303-326
CrossRef156
E Michael Lewiecki. (2009) Is denosumab better than alendronate in the treatment of osteoporosis?. Nature Clinical Practice Rheumatology 5:2, 72-73
CrossRef157
E. Romas. (2009) Clinical applications of RANK-ligand inhibition. Internal Medicine Journal 39:2, 110-116
CrossRef158
M. Sosa Henríquez, D. Hernández Hernández. (2009) Tratamiento de las osteoporosis. Revista Clínica Española 209, 41-47
CrossRef159
John M. Norian, Gohar Zeitlian, Goli Adel, Ruth G. Freeman, Nanette F. Santoro, Lubna Pal. (2009) Low serum osteoprotegerin levels in premenopausal infertile women with low bone density: an association of relevance?. Fertility and Sterility 91:2, 542-548
CrossRef160
Jetae WOO, Takayuki YONEZAWA, Kazuo NAGAI. (2009) KAGAKU TO SEIBUTSU 47:1, 51-58
CrossRef161
Michael T. McDermott. 2009. Osteoporosis. , 89-98.
CrossRef162
Hans-Jürgen Gober, Hiroshi Takayanagi. (2009) The interactions and shared mechanisms of T cells and osteoclasts. Inflammation and Regeneration 29:4, 239-248
CrossRef163
E Michael Lewiecki. (2009) Denosumab for the treatment of postmenopausal osteoporosis. Women's Health 5:1, 15-22
CrossRef164
Jacques P Brown, Richard L Prince, Chad Deal, Robert R Recker, Douglas P Kiel, Luiz H de Gregorio, Peyman Hadji, Lorenz C Hofbauer, Jose M Álvaro-Gracia, Huei Wang, Matthew Austin, Rachel B Wagman, Richard Newmark, Cesar Libanati, Javier San Martin, Henry G Bone. (2009) Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial*. Journal of Bone and Mineral Research 24:1, 153-161
CrossRef165
T. Segovia-Silvestre, A. V. Neutzsky-Wulff, M. G. Sorensen, C. Christiansen, J. Bollerslev, M. A. Karsdal, K. Henriksen. (2009) Advances in osteoclast biology resulting from the study of osteopetrotic mutations. Human Genetics 124:6, 561-577
CrossRef166
Kazuyoshi SAITO, Yoshiya TANAKA. (2009) New biologic and non biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis. Japanese Journal of Clinical Immunology 32:3, 149-159
CrossRef167
Georg Schett, Jean-Pierre David. (2008) Denosumab—a novel strategy to prevent structural joint damage in patients with RA?. Nature Clinical Practice Rheumatology 4:12, 634-635
CrossRef168
P. Szulc, P. D. Delmas. (2008) Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporosis International 19:12, 1683-1704
CrossRef169
Pete Anderson, Lisa Kopp, Nicholas Anderson, Kathleen Cornelius, Cynthia Herzog, Dennis Hughes, Winston Huh. (2008) Novel bone cancer drugs: investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma). Expert Opinion on Investigational Drugs 17:11, 1703-1715
CrossRef170
Evangelos Terpos, Dimitrios Christoulas, Meletios-Athanassios Dimopoulos. (2008) Antibodies to receptor activator of nuclear factor-κ B ligand (RANKL). Expert Opinion on Therapeutic Patents 18:11, 1265-1269
CrossRef171
Andreas Leibbrandt, Josef M. Penninger. (2008) RANK/RANKL: Regulators of Immune Responses and Bone Physiology. Annals of the New York Academy of Sciences 1143:1, 123-150
CrossRef172
Paul D. Miller. (2008) Anti-resorptives in the management of osteoporosis. Best Practice & Research Clinical Endocrinology & Metabolism 22:5, 849-868
CrossRef173
Ian R. Reid. (2008) Anti-resorptive therapies for osteoporosis. Seminars in Cell & Developmental Biology 19:5, 473-478
CrossRef174
Michael T Yin, Elizabeth Shane, Kathryn Anastos. (2008) Clinical significance of HIV-associated bone loss: when and how to intervene. Future HIV Therapy 2:5, 465-478
CrossRef175
Mary L Bouxsein, Pierre D Delmas. (2008) Considerations for Development of Surrogate Endpoints for Antifracture Efficacy of New Treatments in Osteoporosis: A Perspective. Journal of Bone and Mineral Research 23:8, 1155-1167
CrossRef176
Steeve Kwan Tat, Jean-Pierre Pelletier, Daniel Lajeunesse, Hassan Fahmi, Nicolas Duval, Johanne Martel-Pelletier. (2008) Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors. Bone 43:2, 284-291
CrossRef177
Nils Lonberg. (2008) Fully human antibodies from transgenic mouse and phage display platforms. Current Opinion in Immunology 20:4, 450-459
CrossRef178
Thomas J. Beck, E. Michael Lewiecki, Paul D. Miller, Dieter Felsenberg, Yu Liu, Beiying Ding, Cesar Libanati. (2008) Effects of Denosumab on the Geometry of the Proximal Femur in Postmenopausal Women in Comparison with Alendronate. Journal of Clinical Densitometry 11:3, 351-359
CrossRef179
Kathryn E Ackerman. (2008) Is denosumab a safe and effective treatment for postmenopausal osteoporosis?. Nature Clinical Practice Endocrinology & Metabolism 4:7, 376-377
CrossRef180
J. F. Aloia, S. Arunabh-Talwar, S. Pollack, J. K. Yeh. (2008) The remodeling transient and the calcium economy. Osteoporosis International 19:7, 1001-1009
CrossRef181
Matthew R. Smith. (2008) Osteoclast targeted therapy for prostate cancer: Bisphosphonates and beyond. Urologic Oncology: Seminars and Original Investigations 26:4, 420-425
CrossRef182
Stuart H Ralston, Anne L Langston, Ian R Reid. (2008) Pathogenesis and management of Paget's disease of bone. The Lancet 372:9633, 155-163
CrossRef183
Sonja Herman, Gerhard Krönke, Georg Schett. (2008) Molecular mechanisms of inflammatory bone damage: emerging targets for therapy. Trends in Molecular Medicine 14:6, 245-253
CrossRef184
Vincenzo Adamo, Nicola Caristi, Marcello Maugeri Saccà, Giuseppa Ferraro, Concetta Arcanà, Roberto Maisano, Daniele Santini, Giuseppe Tonini. (2008) Current knowledge and future directions on bisphosphonate-related osteonecrosis of the jaw in cancer patients. Expert Opinion on Pharmacotherapy 9:8, 1351-1361
CrossRef185
(2008) Second meeting on bone quality, Abbaye des Vaux de Cernay, France, 19–20 June 2007: Cortical bone. Osteoporosis International 19:6, 853-893
CrossRef186
Hirschhorn, Joel N., Gennari, Luigi, . (2008) Bona Fide Genetic Associations with Bone Mineral Density. New England Journal of Medicine 358:22, 2403-2405
Full Text187
Stanley B. Cohen, Robin K. Dore, Nancy E. Lane, Peter A. Ory, Charles G. Peterfy, John T. Sharp, Désirée van der Heijde, Lifen Zhou, Wayne Tsuji, Richard Newmark, . (2008) Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis & Rheumatism 58:5, 1299-1309
CrossRef188
J. Chris Gallagher. (2008) Advances in bone biology and new treatments for bone loss. Maturitas 60:1, 65-69
CrossRef189
Michael S Ominsky, Xiaodong Li, Frank J Asuncion, Mauricio Barrero, Kelly S Warmington, Denise Dwyer, Marina Stolina, Zhaopo Geng, Mario Grisanti, Hong-Lin Tan, Timothy Corbin, James McCabe, William S Simonet, Hua Z Ke, Paul J Kostenuik. (2008) RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats. Journal of Bone and Mineral Research 23:5, 672-682
CrossRef190
J. González Macías, N. Guañabens Gay, C. Gómez Alonso, L. del Río Barquero, M. Muñoz Torres, M. Delgado, L. Pérez Edo, J. Bernardino Díaz López, E. Jódar Gimeno, F. Hawkins Carranza. (2008) Guías de práctica clínica en la osteoporosis posmenopáusica, glucocorticoidea y del varón. Sociedad Española de Investigación Ósea y del Metabolismo Mineral. Revista Clínica Española 208, 1-24
CrossRef191
JB Richards, F Rivadeneira, M Inouye, TM Pastinen, N Soranzo, SG Wilson, T Andrew, M Falchi, R Gwilliam, KR Ahmadi, AM Valdes, P Arp, P Whittaker, DJ Verlaan, M Jhamai, V Kumanduri, M Moorhouse, JB van Meurs, A Hofman, HAP Pols, D Hart, G Zhai, BS Kato, BH Mullin, F Zhang, P Deloukas, AG Uitterlinden, TD Spector. (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. The Lancet 371:9623, 1505-1512
CrossRef192
S. A. J. Lloyd, Y. Y. Yuan, P. J. Kostenuik, M. S. Ominsky, A. G. Lau, S. Morony, M. Stolina, F. J. Asuncion, Ted A. Bateman. (2008) Soluble RANKL Induces High Bone Turnover and Decreases Bone Volume, Density, and Strength in Mice. Calcified Tissue International 82:5, 361-372
CrossRef193
Y. Y. Yuan, P. J. Kostenuik, M. S. Ominsky, S. Morony, S. Adamu, D. T. Simionescu, D. M. Basalyga, F. J. Asuncion, T. A. Bateman. (2008) Skeletal deterioration induced by RANKL infusion: a model for high-turnover bone disease. Osteoporosis International 19:5, 625-635
CrossRef194
Ronald D Emkey. (2008) Quarterly intravenous ibandronate for postmenopausal osteoporosis. Women's Health 4:3, 219-228
CrossRef195
L. Silva, M. Fernandez-Castro, J.-L. Andreu. (2008) Repairing erosions in rheumatoid arthritis. A realistic goal. Rheumatology 47:9, 1432-1433
CrossRef196
Pierre D. Delmas. (2008) Clinical Potential of RANKL Inhibition for the Management of Postmenopausal Osteoporosis and Other Metabolic Bone Diseases. Journal of Clinical Densitometry 11:2, 325-338
CrossRef197
Allan Lipton. 2008. The Role of Bisphosphonates to Preserve Bone Health in Patients with Breast Cancer. , 1-16.
CrossRef198
B. G. Choi, G. Vilahur, L. Cardoso, J. C. Fritton, B. Ibanez, M. U. Zafar, D. Yadegar, W. S. Speidl, M. B. Schaffler, V. Fuster, J. J. Badimon. (2008) Ovariectomy increases vascular calcification via the OPG/RANKL cytokine signalling pathway. European Journal of Clinical Investigation 38:4, 211-217
CrossRef199
E. Michael Lewiecki, John P. Bilezikian, Cyrus Cooper, Marc C. Hochberg, Marjorie M. Luckey, Michael Maricic, Paul D. Miller. (2008) Proceedings of the Eighth Annual Santa Fe Bone Symposium, August 3–4, 2007. Journal of Clinical Densitometry 11:2, 313-324
CrossRef200
Sheila A Doggrell. (2008) New horizons for zoledronic acid: results of the HORIZON trials in postmenopausal women with osteoporosis and after hip fracture. Expert Opinion on Pharmacotherapy 9:4, 663-668
CrossRef201
I. Byrjalsen, D. J. Leeming, P. Qvist, C. Christiansen, M. A. Karsdal. (2008) Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies. Osteoporosis International 19:3, 339-348
CrossRef202
Roger H. Weenig. (2008) Pathogenesis of calciphylaxis: Hans Selye to nuclear factor κ-B. Journal of the American Academy of Dermatology 58:3, 458-471
CrossRef203
Ron S. Israeli, Christopher W. Ryan, Laura L. Jung. (2008) Managing Bone Loss in Men With Locally Advanced Prostate Cancer Receiving Androgen Deprivation Therapy. The Journal of Urology 179:2, 414-423
CrossRef204
Sengen Sun. (2008) Bone disease drug discovery: examining the interactions between osteoblast and osteoclast. Expert Opinion on Therapeutic Targets 12:2, 239-251
CrossRef205
Anne Fouque-Aubert, Roland Chapurlat. (2008) Influence of RANKL inhibition on immune system in the treatment of bone diseases. Joint Bone Spine 75:1, 5-10
CrossRef206
ALLEN W. ROOT, FRANK B. DIAMOND. 2008. Disorders of Mineral Homeostasis in the Newborn, Infant, Child, and Adolescent. , 686-769.
CrossRef207
Morten A Karsdal, Kim Henriksen, Michel Arnold, Claus Christiansen. (2008) Calcitonin ??? A Drug of the Past or for the Future?. BioDrugs 22:3, 137-144
CrossRef208
Josef S Smolen, Daniel Aletaha, Marcus Koeller, Michael H Weisman, Paul Emery. (2007) New therapies for treatment of rheumatoid arthritis. The Lancet 370:9602, 1861-1874
CrossRef209
Adolfo Díez Pérez. (2007) Aspectos terapéuticos de la osteoporosis. Medicina Clínica 129:20, 773-774
CrossRef210
William C Dougall. (2007) RANKL signaling in bone physiology and cancer. Current Opinion in Supportive and Palliative Care 1:4, 317-322
CrossRef211
E Michael Lewiecki, Paul D Miller, Michael R McClung, Stanley B Cohen, Michael A Bolognese, Yu Liu, Andrea Wang, Suresh Siddhanti, Lorraine A Fitzpatrick. (2007) Two-Year Treatment With Denosumab (AMG 162) in a Randomized Phase 2 Study of Postmenopausal Women With Low BMD. Journal of Bone and Mineral Research 22:12, 1832-1841
CrossRef212
Gregory R. Mundy. (2007) Osteoporosis and Inflammation. Nutrition Reviews 65, S147-S151
CrossRef213
Jaroslav Blahoš. (2007) Treatment and prevention of osteoporosis. Wiener Medizinische Wochenschrift 157:23-24, 589-592
CrossRef214
Shafaat A. Rabbani, Andrew P. Mazar. (2007) Evaluating distant metastases in breast cancer: from biology to outcomes. Cancer and Metastasis Reviews 26:3-4, 663-674
CrossRef215
Juliet Compston. (2007) Over-suppression of bone turnover: Does it exist?. Current Osteoporosis Reports 5:4, 179-185
CrossRef216
Gayatri Gupta, Wilbert S. Aronow. (2007) Treatment of Postmenopausal Osteoporosis. Comprehensive Therapy 33:3, 114-119
CrossRef217
E. Michael Lewiecki. (2007) Long dosing intervals in the treatment of postmenopausal osteoporosis. Current Medical Research and Opinion 23:11, 2617-2625
CrossRef218
Jun Iwamoto, Tsuyoshi Takeda, Yoshihiro Sato. (2007) Effects of antifracture drugs in postmenopausal, male and glucocorticoid-induced osteoporosis – usefulness of alendronate and risedronate. Expert Opinion on Pharmacotherapy 8:16, 2743-2756
CrossRef219
Jean-Pierre Devogelaer, Daniel H Manicourt. (2007) Zoledronic acid for treatment of Paget's disease of bone. Expert Opinion on Pharmacotherapy 8:16, 2863-2869
CrossRef220
T. J. Martin, K. W. Ng. (2007) New Agents for the Treatment of Osteoporosis. International Bone and Mineral Society Knowledge Environment 4:11, 287-298
CrossRef221
Aya Jakobovits, Rafael G Amado, Xiaodong Yang, Lorin Roskos, Gisela Schwab. (2007) From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. Nature Biotechnology 25:10, 1134-1143
CrossRef222
Xiaozhe Han, Toshihisa Kawai, Martin A. Taubman. (2007) Interference with immune-cell-mediated bone resorption in periodontal disease. Periodontology 2000 45:1, 76-94
CrossRef223
Hosam K. Kamel. (2007) Update on Osteoporosis Management in Long-term Care: Focus on Bisphosphonates. Journal of the American Medical Directors Association 8:7, 434-440
CrossRef224
Andrew Grey. (2007) Emerging pharmacologic therapies for osteoporosis. Expert Opinion on Emerging Drugs 12:3, 493-508
CrossRef225
Deborah A. Bradley, Maha Hussain, Robert S. DiPaola, Philip Kantoff. (2007) Bone Directed Therapies for Prostate Cancer. The Journal of Urology 178:3, S42-S48
CrossRef226
Gretchen A. Gignac, Michael J. Morris, Maha Hussain. (2007) Castration Resistant, Taxane Naïve Metastatic Prostate Cancer: Current Clinical Approaches and Future Directions. The Journal of Urology 178:3, S30-S35
CrossRef227
Juliet Compston. (2007) Parathyroid hormone (1–84): new clinical perspectives for treating patients at high-risk of fractures. Expert Review of Obstetrics & Gynecology 2:5, 577-585
CrossRef228
Rajesh Gutta, Patrick J. Louis. (2007) Bisphosphonates and osteonecrosis of the jaws: Science and rationale. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 104:2, 186-193
CrossRef229
Mone Zaidi. (2007) Skeletal remodeling in health and disease. Nature Medicine 13:7, 791-801
CrossRef230
Michael Maricic. (2007) New and emerging treatments for osteoporosis. Current Opinion in Rheumatology 19:4, 364-369
CrossRef231
Lawrence G. Raisz. (2007) The osteoporosis revolution marches on. Journal of Orthopaedic Science 12:4, 405-412
CrossRef232
Nicholas S Chew, Peter P Doran, William G Powderly. (2007) Osteopenia and osteoporosis in HIV: pathogenesis and treatment. Current Opinion in HIV and AIDS 2:4, 318-323
CrossRef233
(2007) Monoclonal Gammopathy of Undetermined Significance. New England Journal of Medicine 356:21, 2223-2224
Full Text234
Natthinee Charatcharoenwitthaya, Sundeep Khosla, Elizabeth J Atkinson, Louise K McCready, B Lawrence Riggs. (2007) Effect of Blockade of TNF-α and Interleukin-1 Action on Bone Resorption in Early Postmenopausal Women. Journal of Bone and Mineral Research 22:5, 724-729
CrossRef235
Cédric Lukas, Bernard Combe, Jacques Morel. (2007) Rheumatoid arthritis and the evolution of therapy: from symptomatic to bench-to-bedside biological drugs. Future Rheumatology 2:2, 143-152
CrossRef236
H J Heller, J E Zerwekh, F A Gottschalk, C Y C Pak. (2007) Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria. Kidney International 71:8, 808-815
CrossRef237
Morten A Karsdal, Thomas J Martin, Jens Bollerslev, Claus Christiansen, Kim Henriksen. (2007) Are Nonresorbing Osteoclasts Sources of Bone Anabolic Activity?. Journal of Bone and Mineral Research 22:4, 487-494
CrossRef238
Hiroshi Takayanagi. (2007) Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nature Reviews Immunology 7:4, 292-304
CrossRef239
Alessandra Sala, Ronald D. Barr. (2007) Osteopenia and cancer in children and adolescents. Cancer 109:7, 1420-1431
CrossRef240
K. Henriksen, L. B. Tanko, P. Qvist, P. D. Delmas, C. Christiansen, M. A. Karsdal. (2007) Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases. Osteoporosis International 18:5, 681-685
CrossRef241
E. Seeman. (2007) Unmet needs in fracture prevention: new European guidelines for the investigation and registration of therapeutic agents. Osteoporosis International 18:5, 569-573
CrossRef242
G Holt, C Murnaghan, J Reilly, R M. D Meek. (2007) The Biology of Aseptic Osteolysis. Clinical Orthopaedics and Related Research PAP,
CrossRef243
Julian MR Mathoo, Lisa Becker, Dinesh Kumbhare, Jonathan D Adachi. (2007) Therapeutic advances in the treatment of osteoporosis. Expert Opinion on Therapeutic Patents 17:3, 277-285
CrossRef244
Georg Schlieper, Ralf Westenfeld, Vincent Brandenburg, Markus Ketteler. (2007) VASCULAR CALCIFICATION IN PATIENTS WITH KIDNEY DISEASE: Inhibitors of Calcification in Blood and Urine. Seminars in Dialysis 20:2, 113-121
CrossRef245
M Baud’huin, L Duplomb, C Ruiz Velasco, Y Fortun, D Heymann, M Padrines. (2007) Key roles of the OPG–RANK–RANKL system in bone oncology. Expert Review of Anticancer Therapy 7:2, 221-232
CrossRef246
Masataka Asagiri, Hiroshi Takayanagi. (2007) The molecular understanding of osteoclast differentiation. Bone 40:2, 251-264
CrossRef247
William C. Dougall, Michelle Chaisson. (2007) The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer and Metastasis Reviews 25:4, 541-549
CrossRef248
Yoshiaki Azuma. (2007) Animal models of osteoporosis and development of anti-osteoporotic agents. Folia Pharmacologica Japonica 130:3, 201-205
CrossRef249
Martina Rauner, Wolfgang Sipos, Peter Pietschmann. (2007) Osteoimmunology. International Archives of Allergy and Immunology 143:1, 31-48
CrossRef250
Daisuke Inoue. (2007) Current and future prospects for anti-osteoporotic drugs. Folia Pharmacologica Japonica 130:3, 206-209
CrossRef251
Pauline M Camacho, Reina Armamento-Villareal, Michael Kleerekoper. (2007) Postmenopausal osteoporosis: an update on current and future therapeutic options. Expert Review of Endocrinology & Metabolism 2:1, 79-90
CrossRef252
Sakae Tanaka. (2007) Signaling Axis in Osteoclast Biology and Therapeutic Targeting in the RANKL/RANK/OPG System. American Journal of Nephrology 27:5, 466-478
CrossRef253
Rana Samadfam, Qingwen Xia, David Goltzman. (2007) Co-Treatment of PTH With Osteoprotegerin or Alendronate Increases Its Anabolic Effect on the Skeleton of Oophorectomized Mice. Journal of Bone and Mineral Research 22:1, 55-63
CrossRef254
B.L. Clarke. (2007) Denosumab in Postmenopausal Women with Low Bone Mineral Density. Yearbook of Endocrinology 2007, 346-347
CrossRef255
E. Seeman. (2006) Reply re: “Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost effective?” by Sanders et al.. Bone 39:6, 1391-1392
CrossRef256
Yutaro Asaba, Kiyoshi Hiramatsu, Yasumoto Matsui, Atsushi Harada, Yuji Nimura, Nobuyoshi Katagiri, Toshihiro Kobayashi, Tsuyoshi Takewaka, Masako Ito, Shumpei Niida, Kyoji Ikeda. (2006) Urinary γ-glutamyltransferase (GGT) as a potential marker of bone resorption. Bone 39:6, 1276-1282
CrossRef257
Jean E Mulder, Nikheel S Kolatkar, Meryl S LeBoff. (2006) Drug Insight: existing and emerging therapies for osteoporosis. Nature Clinical Practice Endocrinology & Metabolism 2:12, 670-680
CrossRef258
Carl T Talmo, Arun S Shanbhag, Harry E Rubash. (2006) Nonsurgical Management of Osteolysis. Clinical Orthopaedics and Related Research 453, 254-264
CrossRef259
Pawel Szulc, Ego Seeman, François Duboeuf, Elisabeth Sornay-Rendu, Pierre D Delmas. (2006) Bone Fragility: Failure of Periosteal Apposition to Compensate for Increased Endocortical Resorption in Postmenopausal Women. Journal of Bone and Mineral Research 21:12, 1856-1863
CrossRef260
Evange Romas, Matthew T. Gillespie. (2006) Inflammation-Induced Bone Loss: Can it Be Prevented?. Rheumatic Disease Clinics of North America 32:4, 759-773
CrossRef261
Stefan Kiechl, Philipp Werner, Michael Knoflach, Martin Furtner, Johann Willeit, Georg Schett. (2006) The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease. Expert Review of Cardiovascular Therapy 4:6, 801-811
CrossRef262
Murray J Favus. (2006) Does denosumab improve low BMD in postmenopausal women?. Nature Clinical Practice Endocrinology & Metabolism 2:11, 600-601
CrossRef263
Laura B Hansen. (2006) Osteoporosis update: effective prevention and treatment. Expert Review of Pharmacoeconomics & Outcomes Research 6:5, 525-540
CrossRef264
E Michael Lewiecki. (2006) RANK ligand inhibition with denosumab for the management of osteoporosis. Expert Opinion on Biological Therapy 6:10, 1041-1050
CrossRef265
Xu Feng. (2006) RANK signaling pathways as potent and specific therapeutic targets for bone erosion in rheumatoid arthritis. Future Rheumatology 1:5, 567-578
CrossRef266
Joseph Michael Lane, Alana Carey Serota. (2006) Osteoporosis therapy. Current Opinion in Orthopaedics 17:5, 451-455
CrossRef267
Mario Eisenberger. (2006) Treatment of Prostate Cancer in the 21st Century—Future Directions. European Urology Supplements 5:15, 824-829
CrossRef268
E. Neumann. (2006) Neue pathophysiologische Stoffwechselwege in der Osteoporose. Zeitschrift für Rheumatologie 65:5, 400-406
CrossRef269
M. R. Smith. (2006) Bisphosphonates for Metastatic Bone Disease -- Too Much of a Good Thing?. International Bone and Mineral Society Knowledge Environment 3:9, 24-27
CrossRef270
Pierre Close, Audrey Neuprez, Jean-Yves Reginster. (2006) Developments in the pharmacotherapeutic management of osteoporosis. Expert Opinion on Pharmacotherapy 7:12, 1603-1615
CrossRef271
E Michael Lewiecki. (2006) Denosumab: a promising drug for the prevention and treatment of osteoporosis. Women's Health 2:4, 517-525
CrossRef272
Kojiro Sato, Hiroshi Takayanagi. (2006) Osteoclasts, rheumatoid arthritis, and osteoimmunology. Current Opinion in Rheumatology 18:4, 419-426
CrossRef273
(2006) Denosumab in Postmenopausal Women with Low Bone Mineral Density. New England Journal of Medicine 354:22, 2390-2391
Full Text274
Sheila A Doggrell. (2006) Inhibition of RANKL: a new approach to the treatment of osteoporosis. Expert Opinion on Pharmacotherapy 7:8, 1097-1100
CrossRef275
R Graham G Russell, Belen Espina, Philippa Hulley. (2006) Bone biology and the pathogenesis of osteoporosis. Current Opinion in Rheumatology 18:Suppl 1, S3-S10
CrossRef276
Marie Lofthouse. (2006) Denosumab improves low BMD in postmenopausal women. Nature Clinical Practice Rheumatology 2:6, 295-295
CrossRef277
Philip Sambrook, Cyrus Cooper. (2006) Osteoporosis. The Lancet 367:9527, 2010-2018
CrossRef278
E. Seeman. (2006) Hot stuff—can’t get enough. Osteoporosis International 17:6, 791-794
CrossRef279
Gherardo Mazziotti, Alberto Angeli, John P. Bilezikian, Ernesto Canalis, Andrea Giustina. (2006) Glucocorticoid-induced osteoporosis: an update. Trends in Endocrinology & Metabolism 17:4, 144-149
CrossRef280
T. J. Martin. (2006) Current, New and Emerging Anti-Resorptive Drugs; Antibody Blockade Of RANKL Action. International Bone and Mineral Society Knowledge Environment 3:5, 42-46
CrossRef281
(2006) In Brief. Nature Reviews Drug Discovery 5:4, 283-283
CrossRef282
Serge Ferrari, Ego Seeman, Gordon J Strewler. (2006) Clinical and basic research papers – February 2006 selections. BoneKEy-Osteovision 3:3, 1-4
CrossRef283
Whyte, Michael P., . (2006) The Long and the Short of Bone Therapy. New England Journal of Medicine 354:8, 860-863
Full Text284
Reynold Spector, Elliot S. Vesell. (2006) The Heart of Drug Discovery and Development: Rational Target Selection. Pharmacology 77:2, 85-92
CrossRef285
Jean-Pierre Devogelaer, Christine Coppin. (2006) Osteogenesis Imperfecta. Treatments in Endocrinology 5:4, 229-242
CrossRef286
Serge Cremers, Patrick Garnero. (2006) Biochemical Markers of Bone Turnover in the Clinical Development of Drugs for Osteoporosis and Metastatic Bone Disease. Drugs 66:16, 2031-2058
CrossRef287
M PILLINGER. (2006) Denosumab in Postmenopausal Women With Low Bone Mineral DensityMcClung MR, for the AMG 162 Bone Loss Study Group (Providence Portland Med Ctr, Ore; et al) N Engl J Med 354:821–831, 2006§. Yearbook of Medicine 2006, 47-48
CrossRef
- Letters
