Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis

In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX(R) scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX(R)-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 +/- 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX(R)-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate

The risk of subsequent osteoporotic fractures is decreased in subjects experiencing fracture while on denosumab: results from the FREEDOM and FREEDOM Extension studies

Bone and mineral researc

Unmet needs and current and future approaches for osteoporotic patients at high risk of hip fracture.

Summary: This review provides a critical analysis of currently available approaches to increase bone mass, structure and strength through drug therapy and of possible direct intraosseous interventions for the management of patients at imminent risk of hip fracture. Purpose : Osteoporotic hip fractures represent a particularly high burden in morbidity-, mortality- and health care-related costs. There are challenges and unmet needs in the early prevention of hip fractures, opening the perspective of new developments for the management of osteoporotic patients at imminent and/or at very high risk of hip fracture. Amongst them, preventive surgical intervention needs to be considered. Methods: A European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)/International Osteoporosis Foundation (IOF) working group reviewed the presently available intervention modalities including preventive surgical options for hip fragility. This paper represents a summary of the discussions. Results: Prevention of hip fracture is currently based on regular physical activity; prevention of falls; correction of nutritional deficiencies, including vitamin D repletion; and pharmacological intervention. However, efficacy of these various measures to reduce hip fractures is at most 50% and may need months or years before becoming effective. To face the challenges of early prevention of hip fractures for osteoporotic patients at imminent and/or at very high risk of hip fracture, preventive surgical intervention needs further investigation. Conclusion: Preventive surgical intervention needs to be appraised for osteoporotic patients at imminent and/or at very high risk of hip fracture

Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

New Selective Estrogen Receptor Modulators (SERMs) in Development

Selective estrogen receptor modulators (SERMs) or estrogen agonists/antagonists have shown promise in osteoporosis in that they have the potential to reduce the risk of fracture, and also reduce the risk of breast cancer. SERMs maybe classified according to their core structure, which is typically a variation of the 17 beta-estradiol template and subclassified according to the side chain at the helix 12 affector region. The best known are the triphenylethylenes such as tamoxifen, used in the management of breast cancer. However, the clinical application of this class of SERMs has been limited due to endometrial stimulation. A second class is the benzothiophenes such as raloxifene and arzoxifene, which have skeletal benefit with little, if any, uterine stimulation. Indole-based SERMs such as bazedoxifene have a 2-phenyl ring system that serves as a core binding unit. Other classes include benzopyrans and naphthalenes (eg, lasofoxifene). In this review article, I will discuss raloxifene and three new SERMs—arzoxifene, bazedoxifene, and lasofoxifene—that have been recently studied. I will discuss their effect on bone, breast, and the cardiovascular system, as well as on safety

Vitamin D inadequacy in Belgian postmenopausal osteoporotic women

BACKGROUND: Inadequate serum vitamin D [25(OH)D] concentrations are associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. The objective of this study is to assess the prevalence of inadequate serum 25(OH)D concentrations in postmenopausal Belgian women. Opinions with regard to the definition of vitamin D deficiency and adequate vitamin D status vary widely and there are no clear international agreements on what constitute adequate concentrations of vitamin D. METHODS: Assessment of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone was performed in 1195 Belgian postmenopausal women aged over 50 years. Main analysis has been performed in the whole study population and according to the previous use of vitamin D and calcium supplements. Four cut-offs of 25(OH)D inadequacy were fixed : < 80 nmol/L, <75 nmol/L, < 50 nmol/L and < 30 nmol/L. RESULTS: Mean (SD) age of the patients was 76.9 (7.5) years, body mass index was 25.7 (4.5) kg/m(2). Concentrations of 25(OH)D were 52.5 (21.4) nmol/L. In the whole study population, the prevalence of 25(OH)D inadequacy was 91.3 %, 87.5 %, 43.1 % and 15.9% when considering cut-offs of 80, 75, 50 and 30 nmol/L, respectively. Women who used vitamin D supplements, alone or combined with calcium supplements, had higher concentrations of 25(OH)D than non-users. Significant inverse correlations were found between age/serum PTH and serum 25(OH)D (r = -0.23/r = -0.31) and also between age/serum PTH and femoral neck BMD (r = -0.29/r = -0.15). There is a significant positive relation between age and PTH (r = 0.16), serum 25(OH)D and femoral neck BMD (r = 0.07). (P < 0.05) Vitamin D concentrations varied with the season of sampling but did not reach statistical significance (P = 0.09). CONCLUSION: This study points out a high prevalence of vitamin D inadequacy in Belgian postmenopausal osteoporotic women, even among subjects receiving vitamin D supplements

Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis

Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women