Risedronate Prevents New Vertebral Fractures in Postmenopausal Women at High Risk

Watts, Nelson B.; Josse, Robert G.; Hamdy, Ronald C.; Hughes, Rodney; Manhart, Michael D.; Barton, Ian; Calligeros, Danny; Felsenberg, Dieter

doi:10.1210/jc.2002-020400

Cited by 103 publications

(52 citation statements)

References 34 publications

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“…Similar consistency of treatment effect among subgroups has been observed with alendronate, risedronate, and strontium ranelate. (4)(5)(6)8,12) We did not observe different effects on new vertebral fracture risk in patients stratified by BMI or renal function as was seen with zoledronic acid. (7) As has been observed in studies with some bisphosphonates, the effect of denosumab therapy on nonvertebral fracture risk was influenced by baseline BMD.…”

Section: Discussionsupporting

confidence: 40%

“…The effect of alendronate, risedronate, and strontium ranelate on vertebral fracture risk was similar among various subgroups of postmenopausal women, including strata of age, BMD, and history of fracture. (4)(5)(6) However, zoledronic acid appeared to be less effective in reducing vertebral fracture risk in older and lighter postmenopausal women and in patients with modest renal impairment. (7) Interactions between treatment and risk factors have been reported with antiresorptive agents on nonvertebral fracture risk.…”

Section: Introductionmentioning

confidence: 99%

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Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

McClung

Boonen

Törring

et al. 2011

Journal of Bone and Mineral Research

137

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Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed ( p > 0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T-score À2.5 but not in those with a T-score > À2.5; in those with a body mass index (BMI) < 25 kg/m 2 but not ! 25 kg/m 2 ; and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline. ß

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Section: Discussionsupporting

confidence: 40%

Section: Introductionmentioning

confidence: 99%

Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

McClung

Boonen

Törring

et al. 2011

Journal of Bone and Mineral Research

137

View full text Add to dashboard Cite

show abstract

“…This results in an increase in BMD and reduction in risk for fracture. (5)(6)(7)(8)(9)(10)(11)(12)(13) Denosumab is a novel antiresorptive agent in late-stage clinical development that also inhibits osteoclast-mediated bone resorption but works through a different pathway than bisphosphonates. Denosumab binds with high affinity and specificity to RANKL, a key mediator of osteoclast differentiation, function, and survival.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effect of Denosumab and Alendronate on Bone Mineral Density and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial

Brown¹,

Prince²,

Deal³

et al. 2008

Journal of Bone and Mineral Research

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Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, doubleblind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score Յ −2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n ‫ס‬ 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n ‫ס‬ 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p Յ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab-and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.

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“…6,7 It has been reported that antibone-resorptive agents suppressed the remodeling of newly regenerated bone at a fracture site. In animal models, one of the most widely used antibone-resorptive agents, bisphosphonate, increased the size and mineral content of the callus and stability at the fracture sites in the processes of fracture repair.…”

mentioning

confidence: 99%

Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill‐hole injuries in mice

Katae

Tanaka

Sakai

et al. 2009

Journal Orthopaedic Research

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It is assumed that there are systemic changes in mineral metabolism during fracture healing that may cause a predisposition to sequential fractures in osteoporotic patients who suffered from previous fractures. Initial therapies for patients with osteoporotic fractures are important to prevent disabilities in daily life consequent to bone and muscle atrophies, and sequential fractures, although systemic and local bone metabolism during fracture healing have not been well understood. We evaluated the effects of bone injury and elcatonin injection as an initial therapy on systemic and local bone turnover and bone wound healing. Two drill holes were made in the diaphysis of the left femur and tibia of 12-week-old male C57BL/6J mice. They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28-day experiment. Urinary crosslinked C-telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle-treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect.

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Risedronate Prevents New Vertebral Fractures in Postmenopausal Women at High Risk

Cited by 103 publications

References 34 publications

Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

Comparison of the Effect of Denosumab and Alendronate on Bone Mineral Density and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial

Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill‐hole injuries in mice

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