Relative Risk Of Vertebral Fracture Research Articles

Economic evaluation of four treatment strategies for postmenopausal patients with osteoporosis and a recent fracture in mainland China: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of four anti-osteoporosis medications (denosumab, zoledronate, teriparatide, and alendronate) for postmenopausal osteoporotic women in mainland China, using a stratified treatment strategy recommended by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE). A microsimulation Markov model was used to compare the cost-effectiveness of the four treatments in postmenopausal osteoporotic patients of different ages (65, 70, 75, and 80 years), with a recent fracture from the Chinese healthcare perspective. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represent the incremental cost per quality-adjusted life-year (QALY) obtained. One-way deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of model findings. Alendronate was dominated by denosumab-to-alendronate and zoledronate at all ages examined, indicating that the costs of the two drugs were lower, but QALYs was greater. However, teriparatide-to-alendronate yielded an ICER of $76,432.07/ QALY, compared with alendronate at age 65, which exceeded the pre-determined willingness-to-pay threshold of $37,653/ QALY. The results were similar at other ages. The DSA showed that the most sensitive parameters were drug efficacy for vertebral and wrist fractures, the relative risk of vertebral fractures, and the persistence of the drugs. The PSA showed that zoledronate had a 100% probability of being the most cost-effective treatment, with a willingness-to-pay threshold of $37,653/ QALY. Stratified treatment based on very high fracture risk is more cost-effective than conventional pills in mainland China. Among the stratified treatments, zoledronate is the optimal option.

Pregnancy in a woman with secondary osteoporosis. A case report

BACKGROUND: Glucocorticoid-induced osteoporosis is one of the most serious complications of prolonged (more than three months) systemic glucocorticoid therapy. Rapid bone loss occurs in the first months of treatment, which is a significant risk factor, especially during pregnancy and lactation. When taking systemic glucocorticoid therapy in a daily dose of 5 mg or more (in prednisone equivalent), the relative risk of vertebral fractures increases by 2.9 times.
 RESULTS: This article examines a clinical case of pregnancy and childbirth of 32-year-old woman diagnosed with secondary complicated osteoporosis during treatment with systemic glucocorticosteroids, who has a history of spine compression fractures during lactation after a previous pregnancy. Vitamin D deficiency was diagnosed and corrected during this pregnancy, which minimized the risk of fractures. A baby was delivered through the birth canal. Bisphosphonate therapy was started six months after birth. No new fractures were diagnosed within two years of observation.
 CONCLUSIONS: The approach to the management, diagnosis and delivery of pregnant patients with secondary osteoporosis treated long-term with glucocorticosteroids should be multidisciplinary. It is imperative to prescribe vitamin D and calcium preparations throughout pregnancy and lactation.

Measurements of Bone Health after Thyroid-Stimulating Suppression Therapy in Postmenopausal Women with Differentiated Thyroid Carcinoma: Bone Mineral Density versus the Trabecular Bone Score

Background: Thyroid-stimulating hormone (TSH) suppression therapy is an important treatment modality for differentiated thyroid carcinoma (DTC), but it increases fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and trabecular bone score (TBS) in postmenopausal DTC patients receiving TSH suppression therapy. Methods: A total of 410 postmenopausal DTC patients who underwent thyroidectomy and had at least two dual-energy X-ray absorptiometry measurements, including a preoperative measurement, were included. Patients who had osteoporosis medication for more than 1 year were classified as ‘patients with osteoporosis’. Results: In patients without osteoporosis, the change in %BMD was similar between TSH suppression (−) and (+) groups, while the decrease in %TBS was significantly greater in the TSH suppression (+) group than that of the TSH suppression (−) group. The relative risk of vertebral fracture was decreased by TBS changes but not by BMD changes. In patients with osteoporosis, both BMD and TBS showed significant increases in the TSH suppression (−) group but not in TSH suppression (+) group. At year 4, TBS was significantly lower in the TSH suppression (+) group than that in the TSH suppression (−) group, while BMD showed no difference between groups. Conclusions: TBS may better reflect bone health than BMD in postmenopausal DTC patients with TSH suppression therapy.

The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone

SummaryThe risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk.IntroductionVertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture.MethodsIn 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture.ResultsMean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13–55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders.ConclusionsThe prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.

Diuretic Use and Risk of Vertebral Fracture in Women

BackgroundVertebral fracture is the most common type of osteoporotic fracture. While thiazide diuretics, which are commonly prescribed for the treatment of hypertension, decrease calciuria, they may also induce hyponatremia, which has been associated with increased vertebral fracture risk. Loop diuretics increase calciuria, which would reduce bone mineral density and increase vertebral fracture risk, but they rarely cause hyponatremia. Recent studies on diuretics and fractures did not include or specifically examine vertebral fracture. The few studies of diuretics and vertebral fracture have been limited by cases defined by self-report or administrative data, relatively small number of cases, study design that was not prospective, and lack of long-term follow-up with updated information on diuretic use. MethodsWe conducted a prospective cohort study of thiazide diuretic use, loop diuretic use, and risk of incident clinical vertebral fracture in 55,780 women, 55-82 years of age, participating in the Nurses' Health Study, without a prior history of any fracture. Diuretic use was assessed by questionnaire every 4 years. Self-reported vertebral fracture was confirmed by medical record review. Cox proportional-hazards models were used to simultaneously adjust for potential confounders. ResultsOur analysis included 420 incident vertebral fracture cases documented between 2002 and 2012. The multivariate-adjusted relative risk of clinical vertebral fracture for women taking thiazides compared with women not taking thiazides was 1.47 (95% confidence interval, 1.18-1.85). The multivariate adjusted relative risk of vertebral fracture for women taking loop diuretics compared with women not taking loop diuretics was 1.59 (95% confidence interval, 1.12-2.25). ConclusionThiazide diuretics and loop diuretics are each independently associated with increased risk of vertebral fracture in women.

PMS30 - Is Denosumab Cost-Effective Compared To Oral Bisphosphonates For The Treatment Of Male Osteoporosis (Mop) In Sweden?

PMS30 IS DENOSUMAB COST-EFFECTIVE COMPARED TO ORAL BISPHOSPHONATES FOR THE TREATMENT OF MALE OSTEOPOROSIS (MOP) IN SWEDEN? Parthan A1, Kruse MM1, Agodoa I2, Tao CY1, Silverman SL3, Orwoll E4 1OptumInsight, Cambridge, MA, USA, 2Amgen Inc., Thousand Oaks, CA, USA, 3CedarsSinai Hospital, Beverly Hills, CA, USA, 4Oregon Health & Science University, Portland, OR, USA OBJECTIVES: Cost-effectiveness of denosumab versus oral bisphosphonates in MOP was evaluated from a third-party payer perspective in Sweden. METHODS: A lifetime cohort Markov model was developed to reflect osteoporotic health states. During each cycle, patients could have a fracture, remain healthy, remain in a post fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Bone mineral density (BMD) improvements have been shown to be similar between MOP and post-menopausal osteoporotic (PMO) populations, and a recent fracture trial showed zoledronate to have effects in men similar to those reported previously in women; therefore efficacy data from PMO women were used. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, and ibandronate. Patients in the model were 65-year-old men, with BMD T-score≤1.90 and prevalent vertebral fracture of 22.7%. In the base-case, the model assumed patients could receive treatment effects up to 2 years after discontinuation (offset time). Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. RESULTS: Total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were €45,118, €45,396, €45,526, and €46,523, respectively. Total QALYs were 9.86, 9.91, 9.85, and 9.83, respectively. Denosumab had an incremental cost-effectiveness ratio (ICER) of €5,283 compared to alendronate and dominated risedronate and ibandronate. Results were most sensitive to changes in relative risk (RR) of hip fracture with denosumab, cost of denosumab and RR of vertebral fracture with denosumab. The probability of denosumab being cost-effective compared to oral bisphosphonates at a threshold of €66,000/QALY was 85.5%. In a sensitivity analysis of offset time of 5 years for oral bisphosphonates, denosumab had an ICER of €10,382 compared to alendronate. CONCLUSIONS: Denosumab is costeffective compared to branded and generic oral bisphosphonates in the Swedish MOP population.

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover

SummaryOsteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels.IntroductionBone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels.MethodsPost-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo.ResultsIn the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290).ConclusionThe vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states.

Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: The eValuation of IBandronate Efficacy (VIBE) database fracture study

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.

Recent developments in the management of postmenopausal osteoporosis with bisphosphonates: enhanced efficacy by enhanced compliance

Bisphosphonates are the current mainstay of treatment for postmenopausal osteoporosis. Although daily oral dosing is effective, it is associated with poor compliance, partly because of the pre and postdose fasting and posture requirements. This negatively impacts treatment outcomes, leading to a reduced clinical benefit. Improved, yet still suboptimal adherence has been noticed with less frequent bisphosphonate dosing e.g. once-weekly and once-monthly oral regimens. The recently approved quarterly intravenous (i.v.) injection regimen of ibandronate and yearly i.v. infusion of zoledronic acid are attractive options in the management of postmenopausal osteoporosis. These regimens may assure quarterly and year long compliance.

Mild prevalent and incident vertebral fractures are risk factors for new fractures

This prospective four-year study indicates that post-menopausal osteoporotic women with mild prevalent and incident vertebral fractures have an increased risk of incident fractures. Mild vertebral fractures are under diagnosed as there is disagreement about their clinical significance. Our aim was to assess the risk of subsequent fractures induced by both prevalent and incident mild vertebral fractures in osteoporotic post-menopausal women. Three thousand three hundred and fifty-eight patients, aged 74 +/- 6 years, with post-menopausal osteoporosis included in the placebo groups of two clinical trials of strontium ranelate were followed for 4 years. A Cox regression model adjusted on age, body mass index and bone mineral density was used to calculate the relative risk (RR) of fracture in subjects with only mild fractures as compared to patients without fracture, and to patients with at least one grade >or= 2 fracture. These calculations were made for prevalent and then incident fractures. The RR of vertebral fracture in 4 years was 1.8 (1.3-2.4) p < 0.001, and 2.7 (2.3-3.3) p < 0.001 for patients having only mild vertebral fractures and at least one grade >or= 2 fracture at baseline respectively. The RR of vertebral fracture in the 3rd and 4th years of follow-up was 1.7 (1.1-2.6) p = 0.01, and 1.9 (1.3-2.6) p < 0.001 for patients having during the first 2 years incident mild fractures only, and for patients having at least one grade >or= 2 incident fracture respectively. The RR of non-vertebral fracture in 4 years was 1.3 (0.9-1.9) p = 0.15 and 1.7 (1.4-2.1) p < 0.001 for patients having only mild or at least one grade >or= 2 vertebral fracture at baseline respectively. For patients aged more than 70 years, these RR were 1.45 (0.99-2.11) (p = 0.06), and 1.72 (1.36-2.18) p < 0.001 respectively. The RR of non-vertebral fracture in the 3rd and 4th years was 1.68 (1.36-2.09) p < 0.001 for patients having at least one grade >or= 2 incident fracture during the 2 first years of follow-up. Mild vertebral fractures are a risk factor for subsequent vertebral and non-vertebral fracture in postmenopausal women with osteoporosis; 1 out of 4 patients with an incident mild vertebral fracture in 2 years will fracture again within the 2 next years.

Fracture risk with intermittent high‐dose oral glucocorticoid therapy

To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs). The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of "current" and "no exposure." The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation. Patients who intermittently received high-dose GCs (daily dose > or =15 mg) and had no or little previous exposure to GCs (cumulative exposure < or =1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a daily dose > or =30 mg and whose cumulative exposure was >5 gm, the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval [95% CI] 2.54-5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49-6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29-25.08). Intermittent use of high-dose oral GCs (daily dose > or =15 mg and cumulative exposure < or =1 gm) may result in a small increased risk of osteoporotic fracture. Conversely, patients who receive several courses of high-dose GCs (daily dose > or =15 mg and cumulative exposure >1 gm) have a substantially increased risk of fracture.

Calcaneous quantitative ultrasound measurements predicts vertebral fractures in idiopathic male osteoporosis

Objectives The aim of this study was to identify the differences in ultrasound bone variables (QUS) and to test the ability to discriminate male patients with and without vertebral fractures. Methods We therefore measured broadband ultrasound attenuation (BUA) and speed of sound (SOS) matched for bone mineral density (BMD) and vertebral deformity in idiopathic male osteoporosis. Results One hundred and seventeen men (age 56.6 range 27–78) were divided into three groups (osteoporosis n = 25, osteopenia n = 58 and age-matched control n = 34) according to BMD T-score by WHO criteria. We found 66 patients (56%) with at least one vertebral deformity during the study. BMD and BUA did not differ, while SOS was lower in osteoporosis ( p < 0.001) and control group ( p < 0.001) between the patients with and without vertebral compression. Strong positive correlation was demonstrated between BUA and BMD (lumbar spine r = 0.44, p < 0.001, femoral neck r = 0.56, p < 0.001, radius r = 0.40, p < 0.001), while similar association between SOS and BMD values was not shown. There was no relationship between the BUA and vertebral fracture risk (Odds ratio: 1.14 95% CI: 0.80–1.61). However, the relative risk of vertebral fracture by SOS was 1.56 (95% CI: 1.08–2.62). Adjusting for age and BMI the risk of vertebral fracture did not change (odds ratio for SOS 1.50 95% CI: 1.02–2.22). After adjustment for BMD SOS was still associated with fracture risk at all measured sites (odds ratio: 1.43, 95% CI: 1.02–2.22; 1.41, 95% CI: 1.02–2.17 and 1.32, 95% CI: 1.02–2.0). Conclusion Our results suggest that BUA values are more closely related to density and structure while SOS values are able to predict fractures.

Strontium ranelate: An increased bone quality leading to vertebral antifracture efficacy at all stages

Strontium ranelate is a new antiosteoporotic treatment with a dual mode of action, both increasing bone formation and decreasing bone resorption, which rebalances bone turnover in favor of bone formation and increases bone strength. The antifracture efficacy of strontium ranelate, 2 g per day orally, in the treatment of postmenopausal osteoporosis has been investigated in a large-scale, international, multicenter, phase 3 program in which more than 7000 patients were recruited. This article deals with the vertebral antifracture efficacy of strontium ranelate in postmenopausal women with osteoporosis. A significant early (after 1 year) and sustained (over 3 years) antifracture efficacy of strontium ranelate, compared with placebo, was demonstrated in patients with prevalent vertebral fracture with reductions in risk of new vertebral fracture of 49% after 1 year ( P < 0.001) and 41% over 3 years ( P < 0.001). In addition, the relative risk of clinical vertebral fracture was significantly reduced by 52% ( P = 0.003) after 1 year and by 38% ( P < 0.001) over 3 years in the strontium ranelate group compared with placebo. Strontium ranelate was also demonstrated to significantly decrease the relative risk of vertebral fractures by 45% ( P < 0.001) in patients without prevalent vertebral fracture over 3 years, vs. placebo. Bone mineral density was linearly increased during 3 years of treatment with strontium ranelate in comparison with placebo. Strontium ranelate was well tolerated throughout the entire duration of the clinical trials. Thus, strontium ranelate, 2 g per day orally, is a new, effective, and safe treatment for postmenopausal patients with osteoporosis, to reduce the vertebral fracture risk in patients with or without a history of vertebral fracture.

Protelos: Nonvertebral and hip antifracture efficacy in postmenopausal osteoporosis

Strontium ranelate is a new treatment for postmenopausal osteoporosis, simultaneously increasing bone formation and decreasing bone resorption, thus rebalancing bone turnover in favor of bone formation. Strontium ranelate was demonstrated to significantly reduce the relative risk of vertebral fracture whatever the severity of the disease. In the TReatment Of Peripheral OSteoporosis (TROPOS) study, the incidence of nonvertebral and hip fractures, following treatment with strontium ranelate (Protelos®, Servier) at a dosage of 2 g/day orally, was assessed over a 3-year period. In this double-blind, placebo-controlled trial, 5091 women with postmenopausal osteoporosis were assigned to either strontium ranelate ( n = 2479) or placebo ( n = 2453) treatment. Overall, the reduction in risk for nonvertebral fractures in patients treated with strontium ranelate was 16% ( P = 0.04) and for major fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle and humerus), it was 19% ( P = 0.031), compared with those treated with placebo. Women with osteoporosis and aged 74 years or more who were treated with strontium ranelate ( n = 982) had a 36% reduction in risk of hip fracture ( P = 0.046) over 3 years compared with those treated with placebo ( n = 995). The difference in bone mineral density between groups was 8.2% for femoral neck and 9.8% for total hip at 3 years. The incidence of adverse events was comparable between groups. The study demonstrates that strontium ranelate treatment offers a safe and effective means of reducing the risk of nonvertebral and hip fractures in postmenopausal women with osteoporosis.

Ranélate de strontium : une nouvelle approche de l'ostéoporose post-ménopausique

Strontium ranelate is a novel antiosteoporotic agent that decreases bone resorption while stimulating bone formation. Two large phase III randomized, placebo-controlled studies have been performed to document its effects on the risks of vertebral and non vertebral fractures in postmenopausal women. In 1649 osteoporotic women with prevalent vertebral fracture enrolled in the SOTI study, strontium ranelate was proven efficient in reducing the risk of incident vertebral fractures and improving quality of life. In 5091 osteoporotic women enrolled in the TROPOS study, a significant reduction was observed in the risk of experiencing a new non-vertebral fracture and major osteoporotic fractures over 3 years. The incidence of hip fracture was significantly decreased in a subgroup of 1977 osteoporotic patients aged 74 years or over. In the TROPOS study, a significant reduction over 3 years of the relative risk of first vertebral fracture was demonstrated in women without prevalent vertebral fracture. Furthermore, strontium ranelate was proven able to decrease the relative risk of vertebral and non vertebral fractures in women aged 80 years and over. In osteopenic patients without prevalent fracture, strontium ranelate was shown to reduce the relative risk of vertebral fracture. Strontium ranelate demonstrated in these studies a very good safety profile.

Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.

Cost effectiveness of raloxifene in the treatment of osteoporosis in Sweden

The Multiple Outcomes of Raloxifene Evaluation (MORE) study showed that treatment with raloxifene reduces the risk of vertebral fracture and breast cancer in postmenopausal women with osteoporosis. Based on the MORE study the aim of the present study was to assess the cost effectiveness of raloxifene (compared with no treatment) for the treatment of osteoporosis in postmenopausal women in Sweden. A revised version of a previously developed computer simulation model was used. The impact of the risk-reducing effect of raloxifene on vertebral fractures and breast cancer on cost effectiveness was analysed using a clinical and a morphometric definition of vertebral fracture. Benefits of raloxifene treatment were measured in quality-adjusted life-years (QALYs) and life-years gained. The study estimated the cost effectiveness mainly from a healthcare perspective but the cost effectiveness taking a societal perspective was also analysed. Intervention costs (in Swedish kronor [SEK] and euros [euro], year 2001 values) in postmenopausal women with a relative risk of vertebral fracture of 2 were SEK372000 (euro40000), SEK303000 (euro33000) and SEK263000 (euro28000) per QALY for women aged 60, 70 and 80 years, at start of treatment, respectively, when the clinical vertebral definition was used. The cost effectiveness using a clinical morphometric vertebral fracture definition was similar to the cost effectiveness using a clinical vertebral fracture definition. In relation to accepted threshold values for cost per QALY in Sweden, this model indicates, with its underlying assumptions and data, that raloxifene (compared with no treatment) is cost effective for the treatment of postmenopausal women at an increased risk of vertebral fracture, from the Swedish healthcare and societal perspectives.

Effects of 4-year treatment with once-weekly clodronate on prevention of corticosteroid-induced bone loss and fractures in patients with arthritis: evaluation with dual-energy X-ray absorptiometry and quantitative ultrasound

The aim of this placebo-controlled study was to determine whether once-weekly clodronate could prevent osteoporosis in patients with arthritis at the start of corticosteroid therapy. One hundred sixty-three patients, 18 to 90 years of age, with rheumatoid or psoriatic arthritis, were randomly assigned to receive either clodronate (100 mg im/week) plus calcium and vitamin D (1000 mg and 800 UI, respectively) or calcium and vitamin D alone. Patients had started therapy with prednisone or its equivalent within the previous 100 days and had bone mineral density <2.5 SD below mean young normal values at the lumbar spine or femoral neck. The primary outcome was the difference between the two treatment groups at months 12, 24, 36, and 48 in the mean percentage change from baseline in the bone mineral density of the lumbar spine, femur (neck and total), and total body. Secondary measurements included changes in the stiffness index evaluated by ultrasound measurements and the rate of new vertebral fractures. The bone density and stiffness did not change significantly in the clodronate plus calcium and vitamin D group, whereas it declined significantly in the calcium plus vitamin D group. The difference between treatment groups at 48 months in the mean change from baseline was 8.78 ± 1.4% for the lumbar spine (P < 0.01), 7.31 ± 1.12% for the femoral neck (P < 0.01), 7.92 ± 1.93% for the trochanter (P < 0.01), 8.39 ± 1.80% for total femur (P < 0.01), 6.94 ± 1.09% for total body (P < 0.01), and 9.38 ± 2.21% for stiffness of os calcis (P < 0.01). Depending on the skeletal regions evaluated, 85 to 98% of patients treated with clodronate had a densitometric change lower than the lowest significant densitometric difference. One hundred percent of patients treated with calcium plus vitamin D had a densitometric decrease greater than the lowest significant difference. The relative risk of vertebral fractures and multiple vertebral fractures in the clodronate group compared to the calcium plus vitamin D group was 0.63 (0.35–0.98, 95% CI) and 0.25 (0.15–0.91, 95% CI), respectively. We concluded that pulsatory administration of im clodronate once weekly is a safe therapy for preventing corticosteroid induced osteoporosis in patients with arthritis.

Antiresorptive Treatment of Postmenopausal Osteoporosis: Comparison of Study Designs and Outcomes in Large Clinical Trials with Fracture as an Endpoint

Antiresorptive treatments for postmenopausal osteoporosis have been studied extensively, but due to the volume of published data and lack of head-to-head trials, it is difficult to evaluate and compare their fracture reduction efficacy. The objective of this review is to summarize the results from clinical trials that have fracture as an endpoint and to discuss the factors in study design and populations that can affect the interpretation of the results. Although there are numerous observational studies suggesting that estrogen and hormone replacement therapies may reduce the risk of vertebral and nonvertebral fractures, there is no large, prospective, randomized, placebo-controlled, double-blind clinical trial demonstrating fracture efficacy. The effects of raloxifene, alendronate, risedronate, and salmon calcitonin on increasing bone mineral density (BMD) and decreasing fracture risk have been shown in randomized, placebo-controlled, double-blind clinical trials of postmenopausal women with osteoporosis. Although the increases in lumbar spine BMD vary greatly in these trials, the decrease in relative risk of vertebral fractures is similar among therapies. However, nonvertebral fracture efficacy has not been consistently demonstrated. Combined administration of two antiresorptive therapies results in greater BMD increases, but the effects on fracture risk are unknown. Direct comparisons of clinical trial results should be considered carefully, given the differences in study design and populations. Differences in study design that may influence the efficacy of fracture risk reduction include calcium and vitamin D supplementation, primary fracture endpoints, definition of vertebral deformity or fracture, discontinuation rates, and statistical power. Factors in the study population that may influence fracture efficacy include the age of the population and the proportion of subjects with prevalent fractures. The use of surrogate endpoints such as BMD to predict fracture risk should be approached with caution, as the relationship between BMD changes and fracture risk reduction with antiresorptive therapies is uncertain. Consideration of these results from clinical trials can contribute to clinical judgment in selecting the best treatment option for postmenopausal osteoporosis.

Prevention of postmenopausal osteoporosis with oestrogen replacement therapy and associated compounds: update on clinical trials since 1995.

Hormonal replacement therapy (HRT) is generally regarded as first choice for pharmacological prevention of osteoporosis in women. We reviewed recent studies of HRT regimens and selective oestrogen receptor modulators (SERMs), including controlled trials of at least one-year duration published since 1995 until February 2000 providing data on bone mineral density (BMD) or fractures. Natural and synthetic oestrogens exert a continuum of positive effects on BMD in a dose-dependent, though non-proportional, fashion independent of age and mode of administration. Bone loss may be largely prevented by 25 microg transdermal patch oestradiol, 0.3 mg conjugated equine or 0.3 mg esterified oestrogens. Progestogens neither attenuate nor augment the effect of oestrogens; sole use of tibolone prevents bone loss. Both the SERMs, tamoxifen and raloxifene, slightly increase BMD. There are no adequately powered fracture trials for any HRT regimen. Raloxifene 60 mg daily decreases the relative risk of vertebral fractures by at least 30%, as demonstrated by one 3-year fracture study of osteoporotic women. In conclusion, the recommendation to use oestrogen for postmenopausal osteoporosis, given both the lack of fracture trials and the rare trials on long-term use of HRT in (late) postmenopausal women, is not well supported. Fracture trials could overcome shortcomings of the current level of evidence.