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The evidence and scientific guidance regarding the efficacy of combination treatment strategies for osteoporosis is currently limited. We performed a systematic review of primary studies that evaluated the effect of combination bone-active medication therapy on BMD and/or fracture outcomes. Eleven studies that assessed 7 different combinations of medications were included. Evidence for superior efficacy of combination treatment compared with monotherapy was strong for only 3 medication combinations: teriparatide and denosumab, teriparatide and zoledronic acid, and alendronate and raloxifene. Three small studies that evaluated combination teriparatide and denosumab found evidence of statistically significant benefit for increasing BMD at the lumbar spine and/or hip more than either medication alone. One large study that evaluated combination teriparatide and zoledronic acid found that after 1 yr of treatment BMD at the lumbar spine increased significantly more in the combination treatment group than the zoledronic acid alone group, and BMD at the hip increased significantly more in the combination treatment group than the teriparatide alone group. This study also found significantly reduced risk of clinical fractures with combination therapy compared with zoledronic acid alone, but not when compared with teriparatide alone. Two studies that evaluated combination alendronate and raloxifene found evidence of significant benefit on BMD outcomes. We found insufficient evidence for superior efficacy of other bone-active medication combinations compared with monotherapy on either BMD outcomes or the very limited data on fracture outcomes. In conclusion, there is evidence supporting the use of combination treatment with teriparatide and denosumab, teriparatide and zoledronic acid, and alendronate and raloxifene for osteoporosis for increasing BMD more than monotherapy, although several of the studies showing benefit of these combinations are small, and data are lacking on fracture outcomes. These combinations can be considered for treatment of patients with osteoporosis; however, further larger studies would be useful to evaluate fracture outcomes as well as other combinations for potential efficacy.

Abstract licence: CC BY

BackgroundThe objective of this study was to conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of various anti-osteoporosis drugs in preventing femoral periprosthetic bone loss following total hip arthroplasty (THA).MethodologyRandomized controlled trials (RCTs) assessing the clinical efficacy of various anti-osteoporosis drugs and control treatments in preventing periprosthetic bone loss following THA were identified. Outcomes evaluated included bone mineral density (BMD) at 6 months, 12 months, 24 months, and 5-10 years. The network meta-analysis was conducted using Stata 13.0 and R-3.5.1 software with the "gemtc" package.ResultsA total of 33 RCTs with 1,169 patients were included. At 6 months, alendronate, alendronate + alfacalcidol, denosumab, ibandronate, raloxifene, teriparatide + alendronate, and zoledronic acid were beneficial in increasing BMD, with denosumab ranking highest (based on surface under the cumulative ranking curve (SUCRA) values). At 12 months, alendronate, alendronate + alfacalcidol, denosumab, ibandronate, risedronate, and zoledronic acid showed benefits, with alendronate + alfacalcidol ranking highest (SUCRA = 0.97). For 24-month BMD, teriparatide + alendronate ranked highest (SUCRA = 0.82). Analysis of BMD at 5-10 years, involving four studies on alendronate, pamidronate, and placebo, indicated that alendronate achieved the highest SUCRA value (0.87).ConclusionBoth denosumab and bisphosphonates are effective in preventing femoral periprosthetic bone loss following THA. Denosumab was the most efficient agent for increasing BMD at 6 months post-THA, while alendronate combined with alfacalcidol or feriparatide was most efficient at 12 months and 24 months. More high-quality direct comparisons and long-term follow-up studies are needed to determine the optimal drug and dosage for THA patients.

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BackgroundBreast cancer is a major global health burden, with hereditary factors such as BRCA1/2 mutations significantly increasing the lifetime risk. This meta-analysis aimed to evaluate the outcomes of selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene as chemopreventive agents for breast cancer risk reduction in BRCA1/2 mutation carriers.MethodsA meta-analysis was conducted according to the PRISMA guidelines. PubMed, Cochrane Library, and MEDLINE databases were searched for relevant studies published between 2000 and 2024. Case-control studies and observational cohort studies examining the use of tamoxifen/raloxifene in BRCA1/2 carriers were included. Data on the incidence and risk ratios of breast cancer were also extracted. Quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was performed using Review Manager (version 5.4.0).ResultsNine studies (13,676 women) were included. Two studies had low risk, and the remaining seven studies had moderate risk, as assessed by the NOS checklist. Pooled analysis showed tamoxifen/raloxifene decreased breast cancer risk compared to controls (RR 0.80, 95% CI 0.72-0.88, p = 0.04). The risk ratio of breast cancer incidence among BRCA1/2 carriers was reduced after tamoxifen use (RR 1.82, 95% CI 1.48-2.23, p ConclusionThis meta-analysis provides evidence that tamoxifen and raloxifene significantly reduce the breast cancer risk in women with BRCA1/2 mutations. Chemoprevention efficacy was similar for both BRCA1 and BRCA2 carriers. Further research is needed to validate these findings and to optimize their use in high-risk populations.

Abstract licence: CC BY-NC-ND