Treatment Of Postmenopausal Osteoporotic Women Research Articles

Comparative efficacy between monoclonal antibodies and conventional drugs in postmenopausal women with osteoporosis: a network meta-analysis.

To evaluate the efficacy of different pharmacological interventions, with emphasis on monoclonal antibodies (McAbs) for the treatment of postmenopausal osteoporotic women. A search of PubMed, Google Scholar, Embase, and the Cochrane Library, as well as China National Knowledge Infrastructure (CNKI) was performed. Data were collected and pooled using Bayesian network meta-analysis (NMA), which conducts both direct and indirect comparisons. The primary outcome was the percentage change in bone mineral density (BMD) in the lumbar spine from baseline to 1 year of treatment. All drugs were ranked based on the surface under the cumulative ranking area (SUCRA). Furthermore, the heterogeneity, consistency, and publication bias of the enrolled literature were assessed. There were 14 randomized controlled trials (RCTs) consisting of 4,881 participants included to compare 11 interventions. Compared with that of a placebo, all the 10 selected therapies showed significant efficacy through changes in BMD ranging from 6.0% to 19.0% (all P<0.01). As the SUCRA values indicated, the therapeutic performance of antibody drugs was better than that of the conventional chemical agents, and blosozumab was the best choice (SUCRA 99.2%) to improve lumbar spine BMD. Novel McAb treatments achieved better therapeutic effects in the treatment of postmenopausal osteoporosis (PMO), especially blosozumab. Further trials are needed to investigate and optimize the delivery strategy of McAbs.

Cost-Effectiveness of Sequential Teriparatide/Alendronate Versus Alendronate-Alone Strategies in High-Risk Osteoporotic Women in the US: Analyzing the Impact of Generic/Biosimilar Teriparatide.

ABSTRACTTeriparatide, currently only available in brand form in the United States, is a costly drug approved for the treatment of postmenopausal osteoporotic women who are at high risk of fracture. Because market exclusivity for brand teriparatide expired in August 2019 in the US, we sought to understand the potential health economic impact of the availability of generic or biosimilar (generic/biosimilar) teriparatide. We examined the cost‐effectiveness of daily teriparatide for 2 years followed by weekly alendronate for 10 years (ie, sequential teriparatide/alendronate) compared with alendronate alone for 10 years in community‐dwelling white osteoporotic women with prior vertebral fracture at ages 65, 70, 75, and 80. Using an updated version of previously validated Markov microsimulation models, we obtained incremental cost‐effectiveness ratios (ICERs) (dollars [$] per quality‐adjusted life year [QALY]) with a willingness‐to‐pay (WTP) of $150,000 per QALY from a societal perspective with a lifelong time horizon. In the base case, we estimated the annual cost of teriparatide to be $20,161, based on the assumption of 10% brand usage (at a cost of $27,618) and 90% generic/biosimilar usage (priced 30% lower than brand). The ICERs of sequential teriparatide/alendronate compared with alendronate alone were greater than $280,000 per QALY at all ages examined. In deterministic sensitivity analyses, results were sensitive to teriparatide's cost, with the cost of a generic/biosimilar product needing to be 65% to 85% lower than brand for sequential teriparatide/alendronate to be cost‐effective. In probabilistic sensitivity analyses, under the assumption that the annual cost of teriparatide was $20,161, the probabilities of sequential teriparatide/alendronate being cost‐effective were less than 4% at a WTP of $150,000 per QALY. In conclusion, among community‐dwelling older osteoporotic women with prior vertebral fracture in the US, even with the potential availability of generic/biosimilar teriparatide, sequential teriparatide/alendronate would not be cost‐effective unless the cost of generic/biosimilar teriparatide were heavily discounted with respect to the current brand cost. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Effect of a sequential treatment combining abaloparatide and alendronate for the management of postmenopausal osteoporosis

ABSTRACTThe recently published results of the sequential treatment of postmenopausal osteoporotic women with subcutaneous abaloparatide (80 µg/day) (ABL) for 18 months followed by 6 months of oral alendronate (70 mg/week) (ALN) support the administration of an anti-resorptive agent after completion of a treatment course with an osteoanabolic agent. The ABL/ALN sequence resulted in greater bone mineral density gains at all skeletal sites and in a reduction of vertebral, non-vertebral, major and clinical fractures compared to what is observed after 18 months of placebo followed by 6 months of ALN. Whereas questions remained unanswered about the ideal anti-resorptive agent to be used after ABL, the optimal duration of the administration of the anti-resorptive drug or the potential interest of re-initiating a course of ABL after a limited administration of ALN, these results support the use of the ABL/ALN sequence in the management of postmenopausal osteoporosis.

Efficacy and safety of Nigella sativa in the treatment of post-menopausal osteoporotic women: a randomized double-blind placebo-controlled trial

Efficacy and safety of Nigella sativa in the treatment of post-menopausal osteoporotic women: a randomized double-blind placebo-controlled trial

Comparative cost-effectiveness of bazedoxifene and raloxifene in the treatment of postmenopausal osteoporosis in Europe, using the FRAX algorithm

Bazedoxifene and raloxifene were evaluated in the treatment of postmenopausal osteoporosis from health economic perspective in Europe. Based on a computer-based algorithm calculating efficacy of the treatments, bazedoxifene appears to be a cost-effective strategy compared to raloxifene, particularly in patients at high fracture risk. The purpose of this study was to compare cost-effectiveness of bazedoxifene and raloxifene in eight European countries: Belgium, France, Germany, Ireland, Italy, Spain, Sweden, and the UK. The Fracture Risk Assessment Tool, which is a computer-based algorithm to calculate fracture probability using clinical risk factors alone or with bone mineral density, was incorporated in a Markov Tunnel model to evaluate cost-effectiveness of bazedoxifene 20 or 40 mg vs. raloxifene 60 mg in postmenopausal osteoporotic women. The efficacy of bazedoxifene and raloxifene for vertebral and non-vertebral fractures was measured as a function of the 10-year probability of a major osteoporotic fracture. The model estimated the incremental cost-effectiveness ratio and net monetary benefit (NMB) from a healthcare perspective, given the willingness to pay <euro>30,000. In postmenopausal osteoporotic women, bazedoxifene was a cost saving strategy compared to raloxifene in the countries studied. The median NMB of bazedoxifene compared to raloxifene increased monotonically with the 10-year fracture probability. In general, the median NMB became greater than 0 in women with 10-year probabilities of a major osteoporotic fracture between 5 and 10% or above. The impact on results by varying the assumptions in the model was examined in sensitivity analysis. Bazedoxifene appears to be a cost-effective strategy compared to raloxifene for the treatment of postmenopausal osteoporotic women in Europe, particularly in patients at high fracture risk.

Cost–effectiveness of denosumab in the treatment of postmenopausal osteoporotic women

Denosumab is a novel biological agent for the treatment of osteoporosis in postmenopausal women with increased risk of fractures. With limited healthcare resources, economic evaluations are increasingly being used by decision-makers to optimize healthcare resource allocation. The cost–effectiveness of denosumab has been evaluated in various studies, and a systematic literature study was conducted up to April 2012 to identify all published research articles and research abstracts presented at various congresses. This article provides a systematic review of four articles and eight abstracts reporting on the cost–effectiveness of denosumab in the treatment of osteoporosis. In most economic evaluations, denosumab has been considered as a cost-effective treatment compared with first-line and second-line options (including generic alendronate) in the treatment of women with high risk of fractures.

Cost-effectiveness of bazedoxifene compared with raloxifene in the treatment of postmenopausal osteoporotic women

Bazedoxifene is a novel selective estrogen receptor modulator (SERM) for the prevention and treatment of osteoporosis. In addition to the therapeutic value of a new agent, evaluation of the cost-effectiveness compared with relevant alternative treatment(s) is an important consideration to facilitate healthcare decision making. This study evaluated the cost-effectiveness of bazedoxifene compared with raloxifene for the treatment of postmenopausal women with osteoporosis. The cost-effectiveness of treatment for 3 years with bazedoxifene was compared with raloxifene using an updated version of a previously validated Markov microsimulation model. Analyses were conducted from a Belgian healthcare payer perspective and, the base-case population was women (aged 70 years) with bone mineral density T-score ≤ -2.5. The effects of bazedoxifene and raloxifene on fracture risk were derived from the 3-year results of a randomized, double-blind, placebo-controlled and active-controlled study, including postmenopausal women with osteoporosis. The cost-effectiveness analysis based on efficacy data from the overall clinical trial indicated that bazedoxifene and raloxifene were equally cost-effective. When the results were examined based on the subgroup analysis of women at higher risk of fractures, bazedoxifene was dominant (lower cost for higher effectiveness) compared with raloxifene in most of the simulations. Sensitivity analyses confirmed the robustness of the results, which were largely independent of starting age of treatment, fracture risk, cost, and disutility. In addition, when the cost of raloxifene was reduced by one-half or when incorporating the raloxifene effects on reducing breast cancer, bazedoxifene remained cost-effective, at a threshold of €35,000 per quality-adjusted life-years gained, in 85% and 68% of the simulations, respectively. Under the assumption of improved antifracture efficacy of bazedoxifene over raloxifene in women with high risk of fractures, this study suggests that bazedoxifene can be considered cost-effective, and even dominant, when compared with raloxifene in the treatment of postmenopausal osteoporotic women.

Cost Effectiveness of Denosumab Compared with Oral Bisphosphonates in the Treatment of Post-Menopausal Osteoporotic Women in Belgium

Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40 000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30 000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or less and no prior fractures. The cost effectiveness of denosumab compared with generic alendronate was estimated at &U20AC;38 514, &U20AC;22 220 and &U20AC;27 862 per QALY for women aged 60, 70 and 80 years, respectively, with T-scores of -2.5 or less. The equivalent values were &U20AC;37 167, &U20AC;19 718 and &U20AC;19 638 per QALY for women with prevalent vertebral fractures. This study suggests, on the basis of currently available data, that denosumab is a cost-effective strategy compared with oral bisphosphonates (including generic alendronate) for the treatment of post-menopausal osteoporotic women, aged ≥60 years in Belgium. Denosumab therefore appears to have the potential to become a first-line treatment for post-menopausal women with osteoporosis. However, further studies would be required to evaluate the long-term safety and adherence of denosumab in real-world clinical practice as well as head-to-head effectiveness compared with oral bisphosphonates.

Strontium is incorporated into mineral crystals only in newly formed bone during strontium ranelate treatment

Strontium ranelate has been shown to increase bone mass in postmenopausal osteoporosis patients and to reduce fracture risk. The aim of this study was to investigate the potential influence of strontium ranelate (Protelos) treatment on human bone tissue characteristics and quality at the micro- and nanostructural levels. We investigated transiliac biopsies from patients treated for 36 months with strontium ranelate or placebo (n = 5 per group) using synchrotron radiation with a microbeam combining scanning small-angle scattering, X-ray diffraction, and fluorescence spectroscopy (SAXS/XRD/XRF) for a detailed characterization of the mineral crystals within the collagenous bone matrix. A scanning procedure allowed the simultaneous determination of maps of the chemical composition together with thickness, length, and lattice spacing of these mineral crystals within each of the 15- or 25-microm-wide pixels in a thin bone section. The fluorescence results show that only bone packets or osteons formed during the strontium ranelate treatment contain significant amounts of strontium and that up to 0.5 of 10 calcium atoms in the mineral crystals are replaced by strontium, as revealed by a corresponding shift in apatite lattice spacing. The thickness and length of the plate-shaped bone mineral crystals were not affected by the strontium ranelate treatment. As a consequence, there was no indication for a change in human bone tissue quality at the nanoscale after a 36-month treatment of postmenopausal osteoporotic women with strontium ranelate, except for a partial replacement of calcium by strontium ions in the hydroxyapatite crystals, only in newly formed bone.

Potential cost-effectiveness of denosumab for the treatment of postmenopausal osteoporotic women

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 6 Months” (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 (€2009) 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 1 year. Uncertainty was investigated using one-way and probabilistic sensitivity analyses. In particular, additional analyses were performed in populations (over 60 years) 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 €28,441. This value decreased to €15,532 and to €11,603 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 €30,000 per QALY gained for women with a BMD T-score ≤−2.5 or prevalent vertebral fracture, over the entire age range examined (60–80 years). 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 60 years 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.

Cost-effectiveness of strontium ranelate versus risedronate in the treatment of postmenopausal osteoporotic women aged over 75 years

ObjectiveTo estimate the cost-effectiveness of strontium ranelate in the treatment of postmenopausal osteoporotic women aged over 75 years. Materials and methodsA 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. ResultsStrontium 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 €11,435 for women with PVF. When compared with no treatment, the costs per QALY gained of strontium ranelate were €15,588 and €7,708 at 75 and 80 years of age for women with osteoporosis; the equivalent values were €16,518 and €6,015 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. ConclusionThe 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.

Safety and efficacy of 36 months treatment of postmenopausal osteoporotic women with PTH (1–84)

detected in osteocytic lacunar walls in cortical bone, the lower affinity compound appeared to penetrate the osteocyte network further from the bone surface or from vascular channel walls than the higher affinity BP. These observations support our hypothesis that mineral affinity can influence the distribution of BPs and related analogues, both on bone surfaces and within the osteocyte canalicular network. Conflict of interest: CE Mckenna, Procter and Gamble, grant research support. CE McKenna, Procter and Gamble, consultant. MJ Rogers, Procter and Gamble, Roche, Novartis, grant research support.

Zolendronate improves bone-densities and micro architectural parameters — A single case study

study [1]. When compared with placebo, histomorphometry showed high rates of bone formation and higher trabecular bone volume with no safety issues in the biopsies of patients who were treated with PTH (1–84). However, there is no information on the long-term safety and efficacy of PTH(1–84) treatment in the skeleton. We report the results of the Treatment Extension Study (TRES), which evaluated the effects of 36 months of daily PTH(1–84) treatment. Methods: 99 patients who had completed 18 months of daily placebo treatment together with daily vitamin D3 (400 IU) and calcium (700 mg) in the TOP study and 18 months of daily PTH(1–84) with or without calcium in the Open Label Extension Study (OLES) were enrolled and continued on the same open label regimen for another 18 months in TRES. There were no placebo-treated patients in TRES. The ITT population for TRES comprised 91 patients and there was an interruption in PTH treatment between OLES and TRES of ∼2 months. Evaluable iliac crest biopsies were collected from 14 patients (none of whom had provided a biopsy previously) after 36 months of PTH(1–84) treatment. Results: There were no histopathological abnormalities in cancellous or cortical bone with PTH(1–84) treatment. This included an absence of osteomalacia, marrow fibrosis or dyscrasias, woven bone, abnormal osteoid, or cortical trabecularisation. Cortical porosity was 5.6%, the same as observed at 18 months in TOP. Measures of cancellous, periosteal and endocortical bone formation were similar to those at 18 months. Structural variables, including trabecular bone volume, number, thickness and cortical thickness were generally similar to or slightly lower than corresponding bone biopsies obtained from patients following 18 months of PTH therapy. Conclusion: Daily treatment of postmenopausal osteoporotic women with PTH(1–84) for 36 months was generally safe and biopsies showed that cancellous and cortical bone appeared entirely normal. The consistency of the biopsy results following 18 and 36 months of PTH treatment suggests that long-term therapy with PTH preserves the initial benefits accrued during initial exposure. 1. Recker RR, et al. Bone 2009;44:113-9. Conflict of interest: None declared.

Review of ibandronate in the treatment of osteoporosis

Several antiresorptive treatments that reduce the risk of osteoporotic fracture are now available, including bisphosphonates. Ibandronate is a new potent bisphosphonate, currently under development, with unique features. In several animal models of human osteoporosis, it has been shown to inhibit bone resorption and improve bone mechanical properties. Ibandronate is more potent than most current bisphosphonates. Several dosages and schedules have been tested in humans. With the oral daily dose of 2.5 mg, a reduction of 62% in the incidence of vertebral fracture has been demonstrated in a randomised, placebo-controlled trial. In the same trial, a reduction of 50% has been observed – for the first time using a bisphosphonate – with an intermittent regimen (20 mg every other day for the first 24 days, followed by 9 weeks without the treatment). In contrast, another randomised, placebo-controlled trial failed to find a significant reduction in vertebral fracture risk using an dose of 1 mg i.v. every 3 months. Thus, ibandronate can be considered as a promising new option for the treatment of postmenopausal osteoporotic women.

Skeletal Benefits of Alendronate: 7-Year Treatment of Postmenopausal Osteoporotic Women

Skeletal Benefits of Alendronate: 7-Year Treatment of Postmenopausal Osteoporotic Women

Use of Bone Alkaline Phosphatase to Monitor Alendronate Therapy in Individual Postmenopausal Osteoporotic Women

Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. Bone ALP decreased significantly from baseline at 3 months (P </=0.0001), reaching a nadir between 3 and 6 months of alendronate therapy. The magnitude of the bone ALP decrease in the treated osteoporotic population was consistent with normalization to premenopausal concentrations. Of the 74 alendronate-treated subjects, 63 (85.1%) demonstrated a decrease from baseline in bone ALP by 6 months that exceeded the least significant change of 25%. The bone ALP decrease from baseline exceeded 25% in 72 (97%) by the end of the study. The bone ALP assay is a sensitive and reliable tool that may be used to monitor the reduction in bone turnover after alendronate therapy in individual postmenopausal osteoporotic women.

Treatment of Postmenopausal Osteoporosis with High Doses of Synthetic Calcitriol

To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 (calcitriol) in the treatment of osteoporosis. Two-year, double-blind, randomized clinical trial. University medical center. Fifty postmenopausal women with vertebral fractures recruited by referral. Calcium intake was adjusted to 25 mmol/d (1000 mg/d) at baseline. Patients were then randomized to treatment with either calcitriol or placebo. During the study, calcium intake was reduced to 15 mmol/d (600 mg/d) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L (less than 11.0 mg/dL) or urine calcium less than 9.96 mmol/d (less than 400 mg/d). After 2 years, the mean dose of calcitriol in the treated group was 0.62 micrograms/d. Bone mineral density of the spine increased 1.94% with calcitriol therapy and decreased 3.92% with placebo (P = 0.001). Total body calcium increased 0.21% with calcitriol therapy and decreased 1.85% with placebo (P = 0.004). Patients receiving placebo had significant decreases in spine density (P = 0.0007) and total body calcium (P = 0.0004). There were no differences in vertebral fracture rates between the groups. Renal function studies were not statistically different between the groups after 2 years. The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium. No adverse effects on renal function were seen after long-term calcitriol therapy.