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Role of Bisphosphonates in The Prevention of Postoperative Hungry Bone Syndrome in Primary Hyperparathyroidism: A Meta-Analysis and Need for Randomized Controlled Trials.
Pal, R, Gautam, A, Bhadada, SK
Drug research. 2021;(2):108-109
Abstract
Dear Editor,Hungry bone syndrome (HBS) is a clinico-biochemical entity characterized by the development of profound and prolonged hypocalcemia associated with hypophosphatemia, hypomagnesemia, and rising alkaline phosphatase which follows curative parathyroidectomy for severe primary and secondary hyperparathyroidism. The prevalence of HBS after parathyroidectomy in primary hyperparathyroidism (PHPT) is variable with several case series from Asia reporting remarkably higher prevalence rates of 24-87% 1.
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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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Minodronate in the treatment of osteoporosis: A systematic review and meta-analysis.
Liu, Q, Chen, D, Ye, Z, Jin, Z, Ma, T, Huang, X
Medicine. 2020;(40):e22542
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BACKGROUND The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis. METHOD The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes. RESULT Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744). CONCLUSION Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).
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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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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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Treatment of Glucocorticoid-Induced Osteoporosis with Bisphosphonates Alone, Vitamin D Alone or a Combination Treatment in Eastern Asians: A Meta-Analysis.
Wang, J, Li, H
Current pharmaceutical design. 2019;(14):1653-1662
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BACKGROUND Glucocorticoid (GC)-induced osteoporosis and fractures have become a serious problem for Eastern Asians. Bisphosphonates (BPs), vitamin D and a combination treatment are effective methods to prevent and treat GC-induced osteoporosis. OBJECTIVE The study aimed to compare the efficacy of BPs, vitamin D and a combination treatment for preventing and managing GC-induced osteoporosis in Eastern Asians. METHODS A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane CENTRAL databases was undertaken for randomized controlled trials (RCTs) on the effect of BPs, vitamin D and the combination treatment on GCs-induced osteoporosis in Eastern Asian populations. Primary outcome measures were the change in bone mineral density (BMD) and bone turnover markers. The final search was performed in March 2019. RESULTS Nine RCTs were included. A total of 545 patients met the inclusion criteria. Compared with vitamin D, BPs and the combination treatment significantly alleviated osteoporosis of the spine and femoral neck in Eastern Asians with GC-induced osteoporosis. At the same time, the change in serum bone-specific alkaline phosphatase (BAP) and serum C-telopeptide of type I collagen (CTX) levels was observed to be significantly less with BPs and the combination treatment with vitamin D alone. No significant difference was found between BPs and the combination treatment in the markers mentioned above. CONCLUSION Compared with vitamin D alone, BPs alone and the combination treatment were significantly effective on Eastern Asians with GC-induced osteoporosis. Compared with the combination treatment, BPs alone were observed to be effective enough to increase the BMDs of the spine and femoral neck on both sides and thus prevent GC-induced osteoporosis in Eastern Asians.
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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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Bisphosphonates for steroid-induced osteoporosis.
Allen, CS, Yeung, JH, Vandermeer, B, Homik, J
The Cochrane database of systematic reviews. 2016;(10):CD001347
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BACKGROUND This is an update of a Cochrane Review first published in 1999. Corticosteroids are widely used in inflammatory conditions as an immunosuppressive agent. Bone loss is a serious side effect of this therapy. Several studies have examined the use of bisphosphonates in the prevention and treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported varying magnitudes of effect. OBJECTIVES To assess the benefits and harms of bisphosphonates for the prevention and treatment of GIOP in adults. SEARCH METHODS We searched CENTRAL, MEDLINE and Embase up to April 2016 and International Pharmaceutical Abstracts (IPA) via OVID up to January 2012 for relevant articles and conference proceedings with no language restrictions. We searched two clinical trial registries for ongoing and recently completed studies (ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal). We also reviewed reference lists of relevant review articles. SELECTION CRITERIA We included randomised controlled trials (RCTs) satisfying the following criteria: 1) prevention or treatment of GIOP; 2) adults taking a mean steroid dose of 5.0 mg/day or more; 3) active treatment including bisphosphonates of any type alone or in combination with calcium or vitamin D; 4) comparator treatment including a control of calcium or vitamin D, or both, alone or with placebo; and 4) reporting relevant outcomes. We excluded trials that included people with transplant-associated steroid use. DATA COLLECTION AND ANALYSIS At least two review authors independently selected trials for inclusion, extracted data, performed 'risk of bias' assessment and evaluated the certainty of evidence using the GRADE approach. Major outcomes of interest were the incidence of vertebral and nonvertebral fractures after 12 to 24 months; the change in bone mineral density (BMD) at the lumbar spine and femoral neck after 12 months; serious adverse events; withdrawals due to adverse events; and quality of life. We used standard Cochrane methodological procedures. MAIN RESULTS We included a total of 27 RCTs with 3075 participants in the review. Pooled analysis for incident vertebral fractures included 12 trials (1343 participants) with high-certainty evidence and low risk of bias. In this analysis 46/597 (or 77 per 1000) people experienced new vertebral fractures in the control group compared with 31/746 (or 44 per 1000; range 27 to 70) in the bisphosphonate group; relative improvement of 43% (9% to 65% better) with bisphosphonates; absolute increased benefit of 2% fewer people sustaining fractures with bisphosphonates (5% fewer to 1% more); number needed to treat for an additional beneficial outcome (NNTB) was 31 (20 to 145) meaning that approximately 31 people would need to be treated with bisphosphonates to prevent new vertebral fractures in one person.Pooled analysis for incident nonvertebral fractures included nine trials with 1245 participants with low-certainty evidence (downgraded for imprecision and serious risk of bias as a patient-reported outcome). In this analysis 30/546 (or 55 per 1000) people experienced new nonvertebral fracture in the control group compared with 29/699 (or 42 per 1000; range 25 to 69) in the bisphosphonate group; relative improvement of 21% with bisphosphonates (33% worse to 53% better); absolute increased benefit of 1% fewer people with fractures with bisphosphonates (4% fewer to 1% more).Pooled analysis on BMD change at the lumbar spine after 12 months included 23 trials with 2042 patients. Eighteen trials with 1665 participants were included in the pooled analysis on BMD at the femoral neck after 12 months. Evidence for both outcomes was moderate-certainty (downgraded for indirectness as a surrogate marker for osteoporosis) with low risk of bias. Overall, the bisphosphonate groups reported stabilisation or increase in BMD, while the control groups showed decreased BMD over the study period. At the lumbar spine, there was an absolute increase in BMD of 3.5% with bisphosphonates (2.90% to 4.10% higher) with a relative improvement of 1.10% with bisphosphonates (0.91% to 1.29%); NNTB 3 (2 to 3). At the femoral neck, the absolute difference in BMD was 2.06% higher in the bisphosphonate group compared to the control group (1.45% to 2.68% higher) with a relative improvement of 1.29% (0.91% to 1.69%); NNTB 5 (4 to 7).Pooled analysis on serious adverse events included 15 trials (1703 participants) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 131/811 (or 162 per 1000) people experienced serious adverse events in the control group compared to 136/892 (or 147 per 1000; range 120 to 181) in the bisphosphonate group; absolute increased harm of 0% more serious adverse events (2% fewer to 2% more); a relative per cent change with 9% improvement (12% worse to 26% better).Pooled analysis for withdrawals due to adverse events included 15 trials (1790 patients) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 63/866 (or 73 per 1000) people withdrew in the control group compared to 76/924 (or 77 per 1000; range 56 to 107) in the bisphosphonate group; an absolute increased harm of 1% more withdrawals with bisphosphonates (95% CI 1% fewer to 3% more); a relative per cent change 6% worse (95% CI 47% worse to 23% better).Quality of life was not assessed in any of the trials. AUTHORS' CONCLUSIONS There was high-certainty evidence that bisphosphonates are beneficial in reducing the risk of vertebral fractures with data extending to 24 months of use. There was low-certainty evidence that bisphosphonates may make little or no difference in preventing nonvertebral fractures. There was moderate-certainty evidence that bisphosphonates are beneficial in preventing and treating corticosteroid-induced bone loss at both the lumbar spine and femoral neck. Regarding harm, there was low-certainty evidence that bisphosphonates may make little or no difference in the occurrence of serious adverse events or withdrawals due to adverse events. We are cautious in interpreting these data as markers for harm and tolerability due to the potential for bias.Overall, our review supports the use of bisphosphonates to reduce the risk of vertebral fractures and the prevention and treatment of steroid-induced bone loss.
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External application of traditional Chinese medicine in the treatment of bone cancer pain: a meta-analysis.
Xiangyong, Y, Zhongsheng, Y, Wenchao, L, Hui, D, Shuzhou, Q, Gang, C, XiaoHui, W, Lian, Z
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2016;(1):11-17
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BACKGROUND Bone cancer pain presents a clinical challenge with limitations of current treatments. Many patients seek additional therapies that may relieve pain. Many external applications of traditional Chinese medicines (EAs-TCMs) have been evaluated in clinical trials, but fewer are known about them outside of China. The objective of this study is to assess the efficacy for bone cancer pain. METHODS A systematic literature search was conducted in seven databases until December 2014 to identify randomized controlled trials (RCTs) about EAs-TCMs in the treatment of bone cancer pain. The primary outcome was total pain relief rate. The secondary outcomes were adverse events at the end of treatment course. The methodological quality of RCTs was assessed independently using six-item criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.2.0. We included any RCTs evaluating an EA-TCM for the treatment of bone cancer pain. We conducted a meta-analysis. RESULTS We included six RCTs with 534 patients. In general, the reporting of methodological issues was poor. Compared with morphine sulfate sustained release tablets (MSSRTs) or radiotherapy or bisphosphonates, we analyzed data from five trials reporting on complete response effect score (relative risk (RR) = 5.38, 95% confidence interval (CI) = 2.80-10.31, P < 0.00001) and partial response (RR = 1.18, 95% CI = 1.02-1.37, P = 0.02) and six trials reporting on total pain relief rate (RR = 1.49, 95% CI = 1.43-1.67, P < 0.00001). Six RCTs showed significant effects of EA-TCM for improving pain relief in patients with bone cancer pain. In addition, no severe adverse events were found. CONCLUSION This systematic review showed positive but weak evidence of EA-TCM for bone cancer pain because of the poor methodological quality and the small quantity of the included trials. Future rigorously designed RCTs are required.
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Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta-analysis.
Toth-Manikowski, SM, Francis, JM, Gautam, A, Gordon, CE
Clinical transplantation. 2016;(9):1090-6
Abstract
Mineral and bone disorders that precede kidney transplantation are exacerbated in the post-transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate-treated kidney transplant recipients through meta-analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow-up duration was more than 6 months. We performed random-effects meta-analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm(2) , 95% CI 0.012-0.099 and 0.053 g/cm(2) , 95% CI 0.032-0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.