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Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials.
Bassatne, A, Bou Khalil, A, Chakhtoura, M, Arabi, A, Van Poznak, C, El-Hajj Fuleihan, G
Metabolism: clinical and experimental. 2022;:154962
Abstract
BACKGROUND Aromatase inhibitors (AIs) are routinely used to treat postmenopausal women with early-stage breast cancer. Although AIs improve breast cancer outcomes, they increase the risk of osteoporosis and fractures. This systematic review and meta-analysis assesses the effect of antiresorptive drugs on AI induced bone loss in postmenopausal women with non-metastatic breast cancer. METHODS We searched four databases until November 4th 2020. We included Randomized controlled trials (RCTs) of antiresorptive drugs in postmenopausal women with breast cancer treated with AI. Two authors screened studies, extracted data and assessed the risk of bias independently and in duplicate. RESULTS We identified 14 RCTs: 7 on zoledronic acid, 6 on oral bisphosphonates and 1 on denosumab. The mean difference in bone mineral density (BMD) was 5% at the lumbar spine and 4% at the total hip, at 12 months, favoring zoledronic acid compared to control. The certainty of the evidence was low for lumbar spine and moderate for total hip BMD. Similarly, the mean difference was 3% at the lumbar spine and 2% at the total hip, favoring oral bisphosphonates with moderate certainty. The mean difference was 6% at the lumbar spine, and 4% at the total hip BMD favoring denosumab compared to placebo. In addition, zoledronic acid resulted in a mean difference in bone turnover marker levels of -35-41%, and the relarive risk for morphometric vertebral fractures was 0.7 [0.3-1.4], compared to control. Denosumab reduced fracture incidence by 50% compared to placebo. CONCLUSION Evidence suggests a protective effect of antiresorptive drugs on BMD and bone turnover markers in postmenopausal women with non-metastatic breast cancer on AI. However, data on fracture risk reduction remains unclear.
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Bisphosphonate Therapy for Treating Osteonecrosis in Pediatric Leukemia Patients: A Systematic Review.
Daneshdoost, SM, El Abiad, JM, Ruble, KJ, Jones, LC, Crane, JL, Morris, CD, Levin, AS
Journal of pediatric hematology/oncology. 2021;(3):e365-e370
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BACKGROUND Despite improved outcomes in children with leukemia, complications such as osteonecrosis are common. We conducted a systematic review to investigate the role of bisphosphonates in reducing pain, improving mobility, and stabilizing lesions in pediatric leukemia survivors. METHODS Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, Cochrane, Web of Science, Scopus, CINAHL, and ClinicalTrials.gov databases. Five of 221 articles retrieved met our inclusion criteria. RESULTS Bisphosphonates, especially when combined with dietary calcium and vitamin D supplements and physical therapy (supplements/PT) were associated with improved pain and mobility in 54% and 50% of patients, respectively. A significantly greater proportion of patients treated with bisphosphonates (83%) reported mild/moderate pain or no pain compared with those with supplements/PT alone (36%) (P<0.001). Sixty-six percent of patients treated with bisphosphonates achieved improved/full mobility compared with 27% of those treated with supplements/PT alone (P=0.02). However, 46% of patients showed progressive joint destruction despite bisphosphonate therapy. No adverse events were reported, except for acute phase reactions to intravenous therapies. CONCLUSIONS Bisphosphonates, when combined with supplements/PT, were associated with less pain and improved mobility, but not prevention of joint destruction in pediatric leukemia patients with osteonecrosis.
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Vitamin D supplement on prevention of fall and fracture: A Meta-analysis of Randomized Controlled Trials.
Thanapluetiwong, S, Chewcharat, A, Takkavatakarn, K, Praditpornsilpa, K, Eiam-Ong, S, Susantitaphong, P
Medicine. 2020;(34):e21506
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BACKGROUND Vitamin D supplement is one of the current possible interventions to reduce fall and fracture. Despite having several studies on vitamin D supplement and fall and fracture reductions, the results are still inconclusive. We conducted a meta-analysis to examine the effect of vitamin D supplement in different forms and patient settings on fall and fracture. METHODS A systematic literature research was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) to compare the effects of vitamin D supplements on fall and fracture outcomes. Random-effect models were used to compute the weighted mean difference for continuous variables and the risk ratio for binary variables. RESULTS Forty-seven RCTs with 58,424 participants were identified reporting on fall outcome. Twenty-four of 47 studies with 40,102 subjects also reported fracture outcome. Major populations were elderly women with age less than 80 years. Overall, vitamin D supplement demonstrated a significant effect on fall reduction, RR = 0.948 (95% CI 0.914-0.984; P = .004, I = 41.52). By subgroup analyses, only vitamin D with calcium supplement significantly reduce fall incidence, RR = 0.881 (95% CI 0.821-0.945; P < .001, I = 49.19). Vitamin D3 supplement decreased incidence of fall but this occurred only when vitamin D3 was supplemented with calcium. Regarding fracture outcome, vitamin D supplement failed to show fracture lowering benefit, RR = 0.949 (95% CI 0.846-1.064; P = .37, I = 37.92). Vitamin D along with calcium supplement could significantly lower fracture rates, RR = 0.859 (95% CI 0.741-0.996; P = .045, I = 25.48). CONCLUSIONS The use of vitamin D supplement, especially vitamin D3 could reduce incidence of fall. Only vitamin D with calcium supplement showed benefit in fracture reduction.
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Effects of teriparatide and bisphosphonate on spinal fusion procedure: A systematic review and network meta-analysis.
Cheng, SH, Kuo, YJ, Chen, C, Kang, YN
PloS one. 2020;(9):e0237566
Abstract
BACKGROUND Giving patients anti-osteoporotic agents peri-operatively is a well-accepted strategy to increase fusion rate and prevent complications. The purpose of this study was to investigate effectiveness of teriparatide and bisphosphonate on fusion surgery of thoracic and lumbar spine. METHODS We searched EMBASE and PubMed for randomized clinical trials (RCTs) and prospective comparative studies using teriparatide or bisphosphonate in peri-operative spinal fusion surgery. Our synthesized data of fusion rate, Oswestry disability index (ODI), and adverse event in contrast-based network meta-analysis. Pooled results were presented in risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). RESULTS Our search hit eight RCTs and three prospective studies with 676 patients receiving spinal surgery. Pooled result showed that teriparatide+Denosumab leads to significantly higher fusion rate than placebo (RR, 2.84; 95% CI: 1.22 to 6.60) and bisphosphonate (RR, 2.59; 95% CI: 1.13 to 5.96). We did not observe significant finding among placebo, teriparatide, and bisphosphonate in the two network models. CONCLUSION This is the first network meta-analysis providing an overview of the use of teriparatide and bisphosphonate for spinal fusion surgery. Teriparatide treatments are worth to be consider for spinal fusion surgery.
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Cumulative network meta-analyses, practice guidelines, and actual prescriptions for postmenopausal osteoporosis: a meta-epidemiological study.
Kataoka, Y, Luo, Y, Chaimani, A, Onishi, A, Kimachi, M, Tsujimoto, Y, Murad, MH, Li, T, Cipriani, A, Furukawa, TA
Archives of osteoporosis. 2020;(1):21
Abstract
UNLABELLED We compared the cumulative network meta-analyses with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. There was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vitamin D and calcium, when we used cumulative NMAs as references. PURPOSE To compare the results of cumulative network meta-analyses (NMAs) with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. METHODS MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to retrieve randomized controlled trials (RCTs) in July 2017. The Agency for Healthcare Research and Quality's National Guideline Clearinghouse and associated society websites were searched to retrieve guidelines in June 2018. We used the Medical Expenditure Panel Survey (MEPS) to analyze prescription data from 1996 to 2015. Two independent investigators selected eligible RCTs. One investigator selected potential eligible guidelines, which were confirmed by another investigator. Two independent investigators extracted data from included RCTs. One investigator extracted recommendations from guidelines, which were confirmed by another investigator. (Registration: UMIN000031894) RESULTS We analyzed data from 1995, 2000, 2005, 2010, and 2015. We chose hip fracture as the primary outcome of cumulative NMAs. We included 51 trials, 17 guidelines, and 5099 postmenopausal osteoporosis patients from the MEPS. Bisphosphonate, including alendronate, and combination of vitamin D and calcium (vDCa) were consistently recommendable from an efficacy viewpoint in NMAs and recommended in guidelines. Alendronate was the most prescribed drug (more than 30% over the observation period); however, vDCa was seldom prescribed. The maximum proportion was 5.3% from 2011 to 2015. CONCLUSIONS In postmenopausal osteoporosis, there was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vDCa, when we used cumulative NMAs as references.
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Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.
Barrionuevo, P, Kapoor, E, Asi, N, Alahdab, F, Mohammed, K, Benkhadra, K, Almasri, J, Farah, W, Sarigianni, M, Muthusamy, K, et al
The Journal of clinical endocrinology and metabolism. 2019;(5):1623-1630
Abstract
BACKGROUND Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.
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Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis.
Thongprayoon, C, Acharya, P, Aeddula, NR, Torres-Ortiz, A, Bathini, T, Sharma, K, Ungprasert, P, Watthanasuntorn, K, Suarez, MLG, Salim, SA, et al
Archives of osteoporosis. 2019;(1):35
Abstract
OBJECTIVE The use of immunosuppressive agents, especially glucocorticoids, are associated with increased risks of bone loss in kidney transplant patients. Denosumab, a potent antiresorptive agent, has been shown to increase bone mineral density (BMD) in patients with CKD. However, its effects on bone metabolism and BMD in kidney transplant patients remain unclear. METHODS A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2018 to identify studies evaluating denosumab's effect on changes in bone metabolism and BMD from baseline to post-treatment course in kidney transplant patients. Study results were pooled and analyzed utilizing random-effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095055). RESULTS Five studies (a clinical trial and four cohort studies) with a total of 162 kidney transplant patients were identified. The majority of patients had a baseline eGFR ≥ 30 mL/min/1.73 m2. After treatment (≥ 6 to 12 months), there were significant increases in BMD with standardized mean differences (SMDs) of 3.26 (95% CI 0.88-5.64) and 1.83 (95% CI 0.43 to 3.22) for lumbar spine and femoral neck, respectively. There were also significant increases in T scores with SMDs of 0.92 (95% CI 0.58 to 1.25) and 1.14 (95% CI 0.17 to 2.10) for lumbar spine and femoral neck, respectively. After treatment, there were no significant changes in serum calcium (Ca) or parathyroid hormone (PTH) from baseline to post-treatment course (≥ 6 months) with mean differences (MDs) of 0.52 (95% CI, - 0.13 to 1.16) mmol/L and - 13.24 (95% CI, - 43.85 to 17.37) ng/L, respectively. The clinical trial data demonstrated more asymptomatic hypocalcemia in the denosumab (12 episodes in 39 patients) than in the control (1 episode in 42 patients) group. From the cohort studies, the pooled incidence of hypocalcemia following denosumab treatment was 1.7% (95% CI 0.4 to 6.6%). All reported hypocalcemic episodes were mild and asymptomatic, but the majority of patients required Ca and vitamin D supplements. CONCLUSION Among kidney transplant patients with good allograft function, denosumab effectively increases BMD and T scores in the lumbar spine and femur neck. From baseline to post-treatment, there are no differences in serum Ca and PTH. However, mild hypocalcemia can occur following denosumab treatment, requiring monitoring and titration of Ca and vitamin D supplements.
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Can Bisphosphonates Prevent Recurrent Fragility Fractures? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Lee, SY, Jung, SH, Lee, SU, Ha, YC, Lim, JY
Journal of the American Medical Directors Association. 2018;(5):384-390.e1
Abstract
OBJECTIVES Although a few trials have explored whether bisphosphonates (BPs) prevented recurrent fragility fractures (FFs), little is known about the secondary preventative effects of BPs. Thus, we performed a meta-analysis to examine the effects of BPs on prevention of subsequent fractures, mortality, and on bone metabolic and functional parameters related to FF. We compared BP and control groups. DESIGN A meta-analysis of randomized controlled trials was conducted. SETTING AND PARTICIPANTS Twelve randomized controlled trials that included 5670 participants investigating the effects of BPs following FF were retrieved from PubMed, Embase, and the Cochrane Library. MEASURES We performed a pairwise meta-analysis using fixed- and random-effects models. RESULTS BPs exhibited significant secondary preventative effects after FF compared with controls [overall standardized mean difference = 0.766; 95% confidence interval (CI) 0.493-1.038; P < .001]. The risks of subsequent fracture (odds ratio = 0.499; 95% CI 0.418-0.596; P < .001) and mortality (odds ratio = 0.662; 95% CI 0.511-0.858; P = .002) decreased in the BP groups. Bone mineral density, bone turnover marker levels, pain at the fracture site, and health-related quality of life also differed significantly between the groups. CONCLUSIONS/IMPLICATIONS Our meta-analysis revealed that BPs administered after FF potentially prevented subsequent fractures and reduced mortality. Positive effects in terms of pain, quality of life, and increased bone mineral density and bone metabolism were also verified regardless of the fracture sites and the administration types (oral or intravenous). Therefore, more active BPs use is recommended to prevent recurrent fragility fractures. LEVEL OF EVIDENCE Level I, meta-analysis.
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Bone Health and Bone-Targeted Therapies for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis.
Alibhai, SMH, Zukotynski, K, Walker-Dilks, C, Emmenegger, U, Finelli, A, Morgan, SC, Hotte, SJ, Tomlinson, GA, Winquist, E
Annals of internal medicine. 2017;(5):341-350
Abstract
BACKGROUND Bone health is a significant concern in men with prostate cancer. PURPOSE To evaluate the effectiveness of drug, supplement, and lifestyle interventions aimed at preventing fracture, improving bone mineral density (BMD), or preventing or delaying osteoporosis in men with nonmetastatic prostate cancer. DATA SOURCES Ovid MEDLINE (1946 to 19 January 2017), EMBASE (1980 to 18 January 2017), and the Cochrane Database of Systematic Reviews (19 January 2017). STUDY SELECTION Randomized trials and systematic reviews of trials that were published in English; involved men with nonmetastatic prostate cancer; and compared bone-targeted therapies with placebo, usual care, or other active treatments. DATA EXTRACTION Two reviewers independently extracted study characteristics and assessed study risk of bias for each outcome. DATA SYNTHESIS Two systematic reviews and 28 reports of 27 trials met inclusion criteria. All trials focused on men with nonmetastatic prostate cancer who were initiating or continuing androgen deprivation therapy (ADT). Bisphosphonates were effective in increasing BMD, but no trial was sufficiently powered to detect reduction in fractures. Denosumab improved BMD and reduced the incidence of new radiographic vertebral fractures in 1 high-quality trial. No trials compared calcium or vitamin D versus placebo. Three lifestyle intervention trials did not show a statistically significant difference in change in BMD between exercise and usual care. LIMITATIONS Most trials were of moderate quality. Only 2 randomized controlled trials were designed to examine fracture outcomes. Potential harms of treatments were not evaluated. CONCLUSION Both bisphosphonates and denosumab improve BMD in men with nonmetastatic prostate cancer who are receiving ADT. Denosumab also reduces risk for radiographic vertebral fractures, based on 1 trial. More trials studying fracture outcomes are needed in this population. PRIMARY FUNDING SOURCE Program in Evidence-Based Care.
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Relationship between baseline characteristics and response to risedronate treatment for osteoporosis: data from three Japanese phase III trials.
Mawatari, T, Muraoka, R, Iwamoto, Y
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017;(4):1279-1286
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UNLABELLED We evaluated the influence of baseline age, bone mineral density (BMD), and serum levels of vitamin D on the response to risedronate treatment. Risedronate consistently increased BMD, but our results suggest vitamin D supplementation may be necessary to achieve optimal treatment effect. Furthermore, early intervention may help prevent bone fractures. INTRODUCTION We aimed to investigate the influence of baseline age, BMD, and vitamin D insufficiency on the response to risedronate treatment. METHODS Data regarding 1447 patients was obtained from the registries of three phase III clinical trials of risedronate. The response to treatment was expressed in terms of BMD increase and occurrence of new vertebral fractures. The patients were stratified by baseline values for age (<65, 65-72, and ≥72 years), lumbar spine BMD T-score (osteoporotic, <-2.5; and non-osteoporotic, ≥- 2.5), and serum levels of 25-hydroxyvitamin D (deficient, <21 ng/mL; and non-deficient, ≥21 ng/mL). RESULTS Risedronate consistently increased lumbar spine BMD in all the groups, with similar percentage and absolute increments in all the age tertiles. The percentage, but not absolute, increment in BMD was significantly higher (p = 0.0003) in the osteoporotic than that in the non-osteoporotic patients (baseline). Of the 1330 patients whose baseline serum levels of 25-hydroxyvitamin D were available, 44.7% had vitamin D deficiency (<20 ng/mL), while 89.2% had insufficiency (<30 ng/mL). The percentage and absolute increments in BMD were lower (p < 0.05 and p < 0.01, respectively) in the vitamin D-deficient than those in the non-deficient patients. New vertebral fractures occurred in 1.5 and 0.8% of the osteoporotic and non-osteoporotic patients, respectively (end of the treatment). CONCLUSIONS Therapeutic response in elderly patients is consistent, but early initiation of risedronate treatment may help prevent fractures. Risedronate-induced increase in BMD is lower in patients with vitamin D deficiency, suggesting that vitamin D supplementation is important to achieve optimal treatment response.