Treatment of osteoporosis in men.
; Reginster, Jean-Yves ; et al
in BONE (2013), 53(1), 134-44
SUMMARY: Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline ... [more ▼]
SUMMARY: Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline) are discussed. INTRODUCTION: Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men and to provide a report by a panel of experts (the authors). METHODS: A debate with an expert panel on preselected topics was conducted. RESULTS AND CONCLUSIONS: Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds. Empirical data in men display similarities with data acquired in women, despite pathophysiological differences, which may not be clinically relevant. Men should receive treatment at a similar 10-year fracture probability as in women. The design of mixed studies may reduce the lag between comparable treatments for osteoporosis in women becoming available in men. [less ▲]Detailed reference viewed: 3 (2 ULg)
Strontium ranelate treatment increases osteoprotegerin serum levels in postmenopausal osteoporotic women
Reginster, Jean-Yves ; Bruyère, Olivier ; COLLETTE, Julien
in BONE (2012), 50Detailed reference viewed: 15 (4 ULg)
Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate.
; ; et al
in BONE (2012), 50
BACKGROUND: We studied 265 men (mean age 56.4years; range 18-83years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate ... [more ▼]
BACKGROUND: We studied 265 men (mean age 56.4years; range 18-83years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate (RIS) in patients either commencing (prednisolone 7.5mg/day or equivalent) (prevention arm, n=88) or continuing glucocorticoid therapy (treatment arm, n=177). METHODS: Patients received either a single ZOL 5mg infusion or RIS 5mg oral daily at randomization, along with calcium (1000mg) and vitamin D (400-1200IU). Primary endpoint: difference in percentage change from baseline in bone mineral density (BMD) at the lumbar spine (LS) at 12months. Secondary endpoints: percentage changes in BMD at total hip (TH) and femoral neck (FN), relative changes in bone turnover markers (beta-CTx and P1NP), and overall safety. FINDINGS: In the treatment subpopulation, ZOL increased LS BMD by 4.7% vs. 3.3% for RIS and at TH the percentage changes were 1.8% vs. 0.2%, respectively. In the prevention subpopulation, bone loss was prevented by both treatments. At LS the percentage changes were 2.5% vs. -0.2% for ZOL vs. RIS and at TH the percentage changes were 1.1% vs. -0.4%, respectively. ZOL significantly increased lumbar spine BMD more than RIS at Month 12 in both the prevention population (p=0.0024) and the treatment subpopulation (p=0.0232) in men. In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum beta-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced beta-CTx at all time-points, and P1NP at Month 3 (p=0.0297) only. Both treatments were well tolerated in men, albeit with a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL. INTERPRETATION: Once-yearly ZOL preserves or increases BMD within 1year to a greater extent than daily RIS in men receiving glucocorticoid therapy. [less ▲]Detailed reference viewed: 17 (3 ULg)
Nitrogen-containing bisphosphonates can inhibit angiogenesis in vivo without the involvement of farnesyl pyrophosphate synthase.
; ; Bellahcene, Akeila et al
in Bone (2011), 48(2), 259-66
Nitrogen-containing bisphosphonates (N-BPs) are widely used to block bone destruction associated with bone metastasis because they are effective inhibitors of osteoclast-mediated bone resorption. More ... [more ▼]
Nitrogen-containing bisphosphonates (N-BPs) are widely used to block bone destruction associated with bone metastasis because they are effective inhibitors of osteoclast-mediated bone resorption. More specifically, once internalized by osteoclasts, N-BPs block the activity of farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. In addition to their antiresorptive activity, preclinical evidence shows that N-BPs have antiangiogenic properties. However, the exact reasons for which N-BPs inhibit angiogenesis remain largely unknown. Using different angiogenesis models, we examined here the effects of zoledronate, risedronate and three structural analogs of risedronate (NE-58025, NE-58051 and NE-10790) with lower potencies to inhibit FPPS activity. Risedronate and zoledronate were much more potent than NE-compounds at inhibiting both endothelial cell proliferation in vitro and vessel sprouting in the chicken egg chorioallantoic membrane (CAM) assay. In addition, only risedronate and zoledronate inhibited the revascularization of the prostate gland in testosterone-stimulated castrated rats. Moreover, as opposed to NE-compounds, risedronate and zoledronate induced intracellular accumulation of isopentenyl pyrophosphate (IPP) in endothelial cells by blocking the activity of the IPP-consuming enzyme FPPS. Thus, these results indicated that N-BPs inhibited angiogenesis in a FPPS-dependent manner. However, drug concentrations used to inhibit angiogenesis, both in vitro and in the CAM and prostate gland assays, were high. In contrast, a low concentration of risedronate (1 muM) was sufficient to inhibit blood vessel formation in the ex vivo rat aortic ring assay. Moreover, NE-58025 (which had a 7-fold lower potency than risedronate to inhibit FPPS activity) was as effective as risedronate to reduce angiogenesis in the rat aortic ring assay. In conclusion, our results suggest that low concentrations of N-BPs inhibit angiogenesis in a FPPS-independent manner, whereas higher drug concentrations were required to inhibit FPPS activity in vivo. [less ▲]Detailed reference viewed: 154 (10 ULg)
Potential cost-effectiveness of denosumab for the treatment of postmenopausal osteoporotic women.
Hiligsmann, Mickaël ; Reginster, Jean-Yves
in BONE (2010), 47
Denosumab has recently been shown to be safe and to significantly reduce the risk of vertebral, hip and non-vertebral fractures in the "Fracture REduction Evaluation of Denosumab in Osteoporosis every ... [more ▼]
Denosumab has recently been shown to be safe and to significantly reduce the risk of vertebral, hip and non-vertebral fractures in the "Fracture REduction Evaluation of Denosumab in Osteoporosis every 6Months" (FREEDOM) Trial. Besides the clinical profile of a new drug, it becomes increasingly important to assess whether the drug represents good value for money. This study aims to examine the potential cost-effectiveness of denosumab in the treatment of postmenopausal osteoporotic women. An updated version of a validated Markov microsimulation model was used to estimate the cost (euro2009) per quality-adjusted life-year (QALY) gained of a 3-year denosumab treatment compared with no treatment. The model was populated with cost and epidemiological data for Belgium from a health-care perspective and the base-case population was defined from the FREEDOM Trial. The effect of denosumab after treatment cessation was conservatively assumed to decline linearly over 1year. Uncertainty was investigated using one-way and probabilistic sensitivity analyses. In particular, additional analyses were performed in populations (over 60years) where osteoporosis medications are currently reimbursed in many European countries, i.e. with bone mineral density (BMD) T-score</=-2.5 or prevalent vertebral fracture. In the base-case analysis, the cost per QALY gained of denosumab compared with no treatment was estimated at euro28,441. This value decreased to euro15,532 and to euro11,603 for women with a BMD T-score of -2.5 or prevalent vertebral fracture, respectively. Additional analyses showed that the cost-effectiveness of denosumab fall below commonly accepted threshold of euro30,000per QALY gained for women with a BMD T-score </=-2.5 or prevalent vertebral fracture, over the entire age range examined (60-80years). The results were robust under a wide range of plausible assumptions. In conclusion, this study suggests, on the basis of currently available data, that denosumab is cost-effective compared with no treatment for postmenopausal Belgian women with low bone mass and who are similar to patients included in the FREEDOM Trial. In addition, denosumab was found to be cost-effective in population currently reimbursed in Europe with T-score</=-2.5 or prevalent vertebral fracture, aged 60years and above. Additional data are needed on the relative cost-effectiveness compared with other anti-osteoporotic agents and on the long-term safety of denosumab. [less ▲]Detailed reference viewed: 48 (3 ULg)
Cost-effectiveness of strontium ranelate versus risedronate in the treatment of postmenopausal osteoporotic women aged over 75 years.
Hiligsmann, Mickaël ; Bruyère, Olivier ; Reginster, Jean-Yves
in Bone (2010), 46(2), 440-6
OBJECTIVE: To estimate the cost-effectiveness of strontium ranelate in the treatment of postmenopausal osteoporotic women aged over 75 years. MATERIALS AND METHODS: A validated Markov microsimulation ... [more ▼]
OBJECTIVE: To estimate the cost-effectiveness of strontium ranelate in the treatment of postmenopausal osteoporotic women aged over 75 years. MATERIALS AND METHODS: A validated Markov microsimulation model with a Belgian payer's perspective estimated the cost per quality-adjusted life-year (QALY) of a 3-year strontium ranelate treatment compared with no treatment and with the bisphosphonate risedronate. Data on the effect of both treatments on fracture risk were taken from the Cochrane Database of Systematic Reviews. Analyses were performed for postmenopausal women aged 75 and 80 years, either with a diagnosis of osteoporosis (i.e. bone mineral density T-score </=-2.5 SD) or with prevalent vertebral fractures (PVF). Parameter uncertainty was evaluated using both one-way and probabilistic sensitivity analyses. RESULTS: Strontium ranelate was dominant (i.e. more effective and less costly) versus risedronate for women with osteoporosis aged over 75 years and for women with PVF aged 80 years. The cost per QALY gained of strontium ranelate compared with risedronate at 75 years of age was euro11,435 for women with PVF. When compared with no treatment, the costs per QALY gained of strontium ranelate were euro15,588 and euro7,708 at 75 and 80 years of age for women with osteoporosis; the equivalent values were euro16,518 and euro6,015 for women with PVF. Probabilistic sensitivity analyses showed that strontium ranelate was generally more cost-effective than risedronate, in the range of 60% in all cases. CONCLUSION: The results of this study suggest that strontium ranelate is a cost-effective strategy, in a Belgian setting, for the treatment of postmenopausal osteoporotic women aged over 75 years. [less ▲]Detailed reference viewed: 34 (5 ULg)
Five years treatment with strontium ranelate reduces vertebral and nonvertebral fractures and increases the number and quality of remaining life-years in women over 80 years of age.
; ; et al
in BONE (2010), 46(4), 1038-42
INTRODUCTION: Longevity has resulted in a greater proportion of the population entering a time of life when increasing bone fragility and falls predispose to fractures, particularly nonvertebral fractures ... [more ▼]
INTRODUCTION: Longevity has resulted in a greater proportion of the population entering a time of life when increasing bone fragility and falls predispose to fractures, particularly nonvertebral fractures. Women over 80 years of age constitute 10% of the population but contribute 30% of all fractures and 60% of all nonvertebral fractures. Despite this, few studies have examined antifracture efficacy of treatments in this high-risk group and none has provided evidence for benefits beyond 3 years. MATERIALS AND METHODS: To determine whether strontium ranelate reduces the risk of vertebral and nonvertebral fractures during 5 years, we analyzed a subgroup of 1489 female patients over 80 years of age (mean 83.5+/-3.0 years) with osteoporosis from the SOTI (spinal osteoporosis therapeutic intervention) and TROPOS (treatment of peripheral osteoporosis) studies randomized to strontium ranelate 2 g/d or placebo. All received a supplement of calcium plus vitamin D. RESULTS: By intention to treat, vertebral fracture risk was reduced by 31% (relative risk, RR=0.69; 95% confidence interval, CI 0.52-0.92), nonvertebral fracture risk by 27% (RR=0.73; 95% CI 0.57-0.95), major nonvertebral fracture risk by 33% (RR=0.67; 95% CI 0.50-0.89) and hip fracture risk by 24% (RR=0.76; 95% CI 0.50-1.15, not significant). Treatment was cost-saving as it decreased cost and increased QALYs and life-years. DISCUSSION: Strontium ranelate safely produced a significant reduction in vertebral and nonvertebral fracture risk during 5 years in postmenopausal women over 80 years of age and was cost saving. [less ▲]Detailed reference viewed: 11 (1 ULg)
Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: the eValuation of IBandronate Efficacy (VIBE) database fracture study
; Reginster, Jean-Yves ; et al
in BONE (2009), 44
The eValuation of IBandronate Efficacy (VIBE) head-to-head database fracture study compared fracture rates between patients treated with monthly ibandronate and weekly oral bisphosphonates (BPs). This ... [more ▼]
The eValuation of IBandronate Efficacy (VIBE) head-to-head database fracture study compared fracture rates between patients treated with monthly ibandronate and weekly oral bisphosphonates (BPs). This large study included women ≥45 years old, newly prescribed monthly oral ibandronate or weekly oral alendronate or risedronate, and without malignancy or Paget's disease of bone. The primary analysis included patients who were adherent to treatment during the first 90 days after the index date. The risks of hip, nonvertebral, vertebral and any clinical fracture were compared using Cox proportional hazards models and adjusted for potential confounding factors. A secondary, “intent-to-treat” analysis included all patients who received at least one BP prescription. Sensitivity analyses based on the primary analysis compared patients receiving ibandronate with patients receiving weekly alendronate or risedronate separately, and explored the effect of excluding patients with potential confounding factors from the analysis. Further sensitivity analyses varied the requirement for adherence during the first 90 days after the index date. The primary analysis population included 7345 monthly ibandronate and 56,837 weekly BP patients. Fracture rates after the 12-month observational period were <2% and fracture risk was not significantly different between patients receiving monthly ibandronate or weekly BPs for hip, nonvertebral or any clinical fracture (adjusted relative risk: hip=1.06, p=0.84; nonvertebral=0.88, p=0.255; any clinical fracture=0.82, p=0.052). Ibandronate patients had a significantly lower risk of vertebral fracture than weekly BP patients (adjusted relative risk 0.36, 95% confidence interval 0.18–0.75, p=0.006). In the secondary, “intent-to-treat” analysis, relative risks of fracture were not significantly different between treatment groups for any fracture type. The results of the sensitivity analyses were generally consistent with the primary analysis. This retrospective cohort study found that patients treated with oral monthly ibandronate or weekly BPs (alendronate and risedronate) had similar, low risks of hip fracture, nonvertebral fracture and any clinical fracture. Ibandronate patients had a significantly lower relative risk of vertebral fracture than weekly BP patients; the clinical implications of these findings require further exploration and validation. [less ▲]Detailed reference viewed: 41 (3 ULg)
Long-term treatment of postmenopausal osteoporosis with strontium ranelate: Results at 8 years.
Reginster, Jean-Yves ; Bruyère, Olivier ; et al
in BONE (2009), 45
OBJECTIVES: Strontium ranelate 2 g/day has proven efficacy against vertebral and nonvertebral fracture over 5 years in postmenopausal osteoporosis, though many women require longer-term treatment. This ... [more ▼]
OBJECTIVES: Strontium ranelate 2 g/day has proven efficacy against vertebral and nonvertebral fracture over 5 years in postmenopausal osteoporosis, though many women require longer-term treatment. This article describes the efficacy, safety, and tolerability of this agent over 8 years. METHODS: Postmenopausal osteoporotic women having participated in the 5-year efficacy trials SOTI and TROPOS were invited to enter a 3-year open-label extension study. The results presented here focus on patients who received strontium ranelate for 8 years. RESULTS: At the extension baseline, the population treated for 8 years (n=879; 79.1+/-5.6 years) had femoral neck T-score of -2.61+/-0.71. The cumulative incidences of new vertebral and nonvertebral fractures (13.7% and 12.0%, respectively) over years 6 to 8 were non-statistically different from the cumulative incidences in the first 3 years of the original studies (11.5% and 9.6%). Lumbar spine, femoral neck, and total hip bone mineral density (BMD) increased throughout the 8-year period. Annual relative change in BMD was significant at every visit, except the 8-year visit for femoral neck and total hip BMD. Strontium ranelate was safe and well tolerated over 8 years. CONCLUSIONS: Long-term treatment with strontium ranelate 2 g/day in postmenopausal osteoporotic women leads to continued increases in BMD at all sites. The data also provide some evidence for a sustained antifracture efficacy. [less ▲]Detailed reference viewed: 80 (31 ULg)
Role of Biochemical Markers of Bone Turnover as Prognostic Indicator of Successful Osteoporosis Therapy
Reginster, Jean-Yves ; Collette, Julien ; et al
in BONE (2008), 42
Most of the currently available anti-osteoporosis medications promptly and significantly influence the rate of bone turnover. Biochemical markers of bone turnover now provide a high sensitivity to change ... [more ▼]
Most of the currently available anti-osteoporosis medications promptly and significantly influence the rate of bone turnover. Biochemical markers of bone turnover now provide a high sensitivity to change, allowing the detection of these bone turnover changes within a couple of weeks. Since the anti-fracture efficacy of inhibitors of bone resorption or stimulators of bone formation appears to be largely independent of baseline bone turnover, biochemical markers do not appear to play a significant role in the selection of one particular drug, for an individual patient. However, there are consistent data showing that short-term changes in biochemical markers of bone turnover may be significant predictors of future changes in bone mineral density or fracture reduction, hence suggesting that bone turnover markers play a significant role in the monitoring of anti-osteoporosis therapy. [less ▲]Detailed reference viewed: 57 (11 ULg)
Creb-1 and Ap-1 Transcription Factors Jund and Fra-2 Regulate Bone Sialoprotein Gene Expression in Human Breast Cancer Cells
Detry, Cédric ; Lamour, Virginie ; Castronovo, Vincenzo et al
in BONE (2008), 42(2), 422-31
Bone sialoprotein (BSP) expression is detected in a variety of human osteotropic cancers. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone ... [more ▼]
Bone sialoprotein (BSP) expression is detected in a variety of human osteotropic cancers. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. In this study, we examined the transcriptional regulation of BSP gene expression in MDA-MB-231 and MCF-7 human breast cancer cells compared with Saos-2 human osteoblast-like cells. BSP human promoter deletion analyses delineated a -56/-84 region, which comprises a cAMP response element (CRE) that was sufficient for maximal promoter activity in breast cancer cell lines. We found that the basic fibroblast growth factor response element (FRE) also located in the proximal promoter was a crucial regulator of human BSP promoter activity in Saos-2 but not in breast cancer cells. Promoter activity experiments in combination with DNA mobility shift assays demonstrated that BSP promoter activity is under the control of the CRE element, through CREB-1, JunD and Fra-2 binding, in MDA-MB-231, MCF-7 and in Saos-2 cells. Forskolin, a protein kinase A pathway activator, failed to enhance BSP transcriptional activity suggesting that CRE site behaves as a constitutive rather than an inducible element in these cell lines. Over-expression of JunD and Fra-2 increased BSP promoter activity and upregulated endogenous BSP protein expression in MCF-7 and Saos-2 cells while siRNA-mediated inhibition of both factors expression significantly reduced BSP protein level in MDA-MB-231. Collectively, these data provide with new transcriptional mechanisms, implicating CREB and AP-1 factors, that control BSP gene expression in breast cancer cells. [less ▲]Detailed reference viewed: 37 (4 ULg)
The role of calcium and vitamin D in the management of osteoporosis.
; ; et al
in BONE (2008), 42(2), 246-9
The role of calcium and vitamin D supplementation in the treatment of osteoporosis has been extensively studied. The aim of this paper was to reach, where possible, consensus views on five key questions ... [more ▼]
The role of calcium and vitamin D supplementation in the treatment of osteoporosis has been extensively studied. The aim of this paper was to reach, where possible, consensus views on five key questions relating to calcium and vitamin D supplementation in the management of osteoporosis. Whereas global strategies that target supplementation to the general population could not be justified in terms of efficacy and health economics, there is a clearer rationale for supplementing patients who are at increased risk of osteoporosis and those who have developed osteoporosis, including those already taking other treatments for osteoporosis. The combination of vitamin D with calcium may be beneficial in terms of efficacy and, perhaps, for optimising adherence. [less ▲]Detailed reference viewed: 19 (2 ULg)
Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis.
; ; et al
in BONE (2008), 42(5), 841-7
A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The ... [more ▼]
A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative. [less ▲]Detailed reference viewed: 25 (2 ULg)
Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis.
; ; et al
in BONE (2008), 43(2), 343-7
Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or ... [more ▼]
Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care. [less ▲]Detailed reference viewed: 34 (13 ULg)
Lifetime absolute risk of hip and other osteoporotic fracture in Belgian women.
Hiligsmann, Mickaël ; Bruyère, Olivier ; Ethgen, Olivier et al
in BONE (2008), 43(6), 991-4
OBJECTIVES: To estimate the lifetime absolute risks of hip and other osteoporotic fracture in Belgian women aged 60 years and to examine the effect of changes in baseline population fracture risk and ... [more ▼]
OBJECTIVES: To estimate the lifetime absolute risks of hip and other osteoporotic fracture in Belgian women aged 60 years and to examine the effect of changes in baseline population fracture risk and changes in life expectancy. MATERIALS AND METHODS: Estimates were performed using a Markov microsimulation model and were based on the incidence of first fracture as well as life expectancy. Baseline scenario included projected mortality rates and increasing fracture incidence by 1% per year. Alternative scenarios were performed on age, life expectancy and trends in fracture incidence. Lifetime fracture risk for osteoporotic population (T-score <or= -2.5) was also estimated. RESULTS: In the baseline scenario, lifetime absolute risks of hip fracture and of any major osteoporotic fracture (hip, clinical vertebral or wrist) were respectively 24.8% and 44.3%. Alternative scenarios showed that when assuming no change of age-specific fracture rates over time, these lifetime risks were 18.3% and 35.2%, while these values were 20.0% and 38.3% assuming no future mortality reductions. For osteoporotic women, these values were respectively 34.5% and 51.5%. CONCLUSION: We conclude that absolute lifetime fracture risks are substantial and that trends in fracture incidence and changes in life expectancy have a marked impact on absolute lifetime fracture risks. [less ▲]Detailed reference viewed: 43 (12 ULg)
Pharmacological effects of tiludronate in horses after long-term immobilization
Delguste, Catherine ; Amory, Hélène ; et al
in BONE (2007), 41(3), 414-421
Introduction: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical ... [more ▼]
Introduction: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical biomarkers of bone metabolism and on bone density and structure in an experimental model of disuse osteoporosis induced by cast application in horses. Methods: Two groups of eight horses were immobilized during 8 weeks. The first group (P-group) received a placebo, and the second group (T-group) received tiludronate 1 mg/kg by slow IV infusion. Both treatments were administered twice, 28 days apart. Immobilization consisted of stall rest with the left forelimb packed in a fiberglass cast. It was followed by a 4-week remobilization period and an 8-week standardized training protocol. One biomarker of bone resorption, the C-telopeptides of type 1 collagen cross-links (CTX-1) and one biomarker of bone formation, the bone isoenzyme of alkaline phosphatase (bone ALP), were assessed. Metacarpus III (MCIII) bone mineral density (BMD) and speed of sound (SOS) were evaluated respectively by dual energy X-ray absorptiometry (DEXA) and quantitative ultrasonography (QUS). Lameness was regularly assessed during the remobilization and training periods. Group- and time-related effects were tested by analysis of variance on repeated measurements. Results: A rapid, transient and significant decrease in CTX-1 concentration was seen after each treatment in the T-group only. No significant differences between groups were seen in the evolution of bone ALP activity. At the end of the experiment, the loss of MCIII BMD measured by DEXA in the immobilized limb was significantly less in the T-group than in the P-group. The MCIII SOS measured by QUS did not significantly vary within or between groups throughout the study. Discussion and conclusions: Tiludronate was found to significantly reduce bone resorption during immobilization, as well as to prevent long-term osteopenia in the immobilized limb. Disuse osteopenia did not affect the lateral superficial cortex of MCIII. (C) 2007 Elsevier Inc. All rights reserved. [less ▲]Detailed reference viewed: 9 (1 ULg)
Managing the osteoporotic patient today
in BONE (2007), 40(5, Suppl. 1), 12-18
as reduced pain and disability. The unique mechanism of action of strontium ranelate corrects bone turnover so that it is rebalanced in favor of bone formation. Double-blind, placebo-controlled studies in ... [more ▼]
as reduced pain and disability. The unique mechanism of action of strontium ranelate corrects bone turnover so that it is rebalanced in favor of bone formation. Double-blind, placebo-controlled studies in postmenopausal osteoporosis show it to be effective in reducing vertebral and hip fracture risks. Treatment efficacy has been documented across a wide range of patient profiles and appears to be independent of all the major determinants of fracture risk, including the severity of the disease at baseline, the number of prevalent fractures, and the age of the patient. This antifracture efficacy translates into clinical benefits, including a reduction in the rate of height loss and an increase in the number of patients free of back pain. Strontium ranelate is also one of the few anti osteoporotic drugs with data to demonstrate an improvement in quality of life indices. The rates of compliance with treatment were over 80% in phase 3 studies, reflecting the tolerability and safety profile and the ease of administration of this agent. Strontium ranelate thus offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal women with osteoporosis fractures. (c) 2007 Elsevier Inc. All rights reserved. [less ▲]Detailed reference viewed: 13 (5 ULg)
Strontium ranelate reduces the urinary level of cartilage degradation biomarker CTX-II in postmenopausal women
; ; et al
in BONE (2007), 40(1), 218-222
Objective: Strontium ranelate significantly decreases the risk of osteoporotic fractures. The objective of the present study was to investigate whether strontium ranclate (2 g/day) also affects cartilage ... [more ▼]
Objective: Strontium ranelate significantly decreases the risk of osteoporotic fractures. The objective of the present study was to investigate whether strontium ranclate (2 g/day) also affects cartilage brakedown as measured by urinary marker of cartilage degradation, designated CTX-II. Methods: A subgroup of 2617 postmenopausal osteoporotic women (aged 75.7 +/- 4.4 years) were selected from the TROPOS phase III study on the basis of a urinary sampling reported at each visit during the first three years of the study. When included in TROPOS, they were randomized to strontium ranelate or placebo in a double-blind fashion for 3 years. A calcium and vitamin D supplement was also provided to the subjects during the study. A marker of collagen type II degradation (CTX-II) corrected for urinary creatinine (CTX-II/cr.) was assessed at regular intervals throughout the study in 1310 patients in strontium ranelate group and 1307 patients in placebo group. Results: The response in CTX-II depended on time (p < 0.0001), and this time dependency differed statistically significantly between groups (time x treatment) (p < 0.0003). In addition, there was a statistically significant difference between treatments (p < 0.0001). The difference in the response of CTX-II/cr. appeared already after three months, with the strontium ranelate-treated subjects having approximately 15-20% lower values than the placebo-treated subjects for the remaining study period (p < 0.0001). Conclusion: Treatment with strontium ranelate significantly decreases urinary excretion of CTX-II, a marker of cartilage destruction. Further studies are warranted to investigate an effect on cartilage formation and symptoms of osteoarthritis. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]Detailed reference viewed: 11 (2 ULg)
Considerations in building the evidence in osteoporosis management
in BONE (2007), 41(S1), 30-31Detailed reference viewed: 11 (5 ULg)