Anti-Osteoporosis Drugs for Overall Mortality in the Old (Ages ≥ 50 Years) and Oldest-Old (Ages ≥ 75): A Systematic Review and Meta-Analysis

Abstract

Background: Findings from recent meta-analyses of anti-osteoporosis drugs have shown that there is no association of anti-osteoporosis drugs with overall mortality, possibly because of population limitations such as age, sex, the presence or absence of fractures, and other parameters, which are associated with increased mortality in the elderly. There is no report about possible associations between anti-osteoporosis drugs and overall mortality in the old (ages ≥ 50 years) or oldest (ages ≥ 75 years) population. The purpose of using anti-osteoporosis drugs is not only to improve bone mineral density and reduce fractures, but also to prolong life expectancy, especially in the old or oldest population. We determined the association between anti-osteoporosis drugs and overall mortality in the old and oldest populations, and determined the effects of different demographic parameters. \n \nMethods: We searched Web of Science, Embase, the Cochrane Database, and PubMed from inception to January 10, 2021, for trials reporting the effects of anti-osteoporosis drugs on overall mortality. The effects of calcium and vitamin D were excluded. We included all randomized trials comparing interventions with different anti-osteoporosis drugs, and we included elderly (ages ≥ 50 years) without other metabolic bone diseases. We pooled data using a fixed effects meta-analysis with weighted mean differences and reported 95% confidence intervals (CIs). We also used the I² statistic to assess heterogeneity in the results of individual studies. The primary endpoint was the total number of people in the drug treatment and placebo groups, and the number of deaths during the follow-up periods.\xa0 \n \nFindings: Of 23,242 citations identified by the search strategy, 25 studies (mean duration: 3.0 years, comprising 93,782 participants; 91.4% women; average age: 73.2 years) met the inclusion criteria. A total of 21 studies were mainly comprised of Caucasians. In 25 studies, anti-osteoporosis drugs included bisphosphonate, selective estrogen receptor modulators (SERMs), parathyroid hormone analogues, receptor-activated nuclear factor-κB ligand inhibitor, anti-sclerostin antibodies. and strontium ranelate. One of the studies used two anti-osteoporosis drugs compared with placebos, while all the other studies used one anti-osteoporosis drug.In the elderly population, anti-osteoporosis drugs did not reduce individual mortalities (weight RR: 0.96; 95% CI: 0.90–1.02), with heterogeneity among trials (I² = 2%, p = 0.43); however, none of the anti-osteoporosis drugs was significantly associated with overall mortality. Stratified analyses were performed according to age and sex, with osteoporosis, and with or without fractures. In different age groups (> 65 years of age, > 75 years of age, and > 80 years of age), the associations between anti-osteoporosis drugs and overall mortalities were not significant. In the female and male groups, none of the associations between anti-osteoporosis drugs and overall mortality were significant. In the with or without osteoporosis groups, these drugs did not reduce overall mortalities. However, these drugs did show reduced mortality (RR: 0.83; 95% CI: 0.70–0.99), but only in the group with fractures. \n \nInterpretation: None of the anti-osteoporosis drugs reduced overall mortality, but in the old population with recent fractures, these drugs showed a reduced overall mortality. The association between anti-osteoporosis drugs and overall mortality did not influence by age and sex. The use of these drugs in the old and oldest populations was safe, and was effective in patients with fractures. \n \nFunding Statement: This work was supported by grants from the Chongqing Health and Family Planning Commission (No. 2015MSXM016), Chongqing Development and Reform Commission (No. [2013] 1420), and National Key Clinical Specialties Construction Program of China (No. [2013] 544). \n \nDeclaration of Interests: None.