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Combination therapy of anabolic agents and bisphosphonates on bone mineral density in patients with osteoporosis: a meta-analysis of randomised controlled trials.

ABSTRACT: OBJECTIVE:We aimed to determine whether the concomitant combination therapy of anabolic agents and bisphosphonates produces more effects on bone mineral density (BMD) than anabolic agents alone in patients with osteoporosis. METHODS:We searched MEDLINE, EMBASE and the Cochrane Library for publications from 1 January 1980 to 1 August 2016 to identify all the randomised controlled trials (RCTs) and quasi-RCTs. The primary outcome was the mean per cent changes in BMD at the lumbar spine, the total hip and the femoral neck with an optimal period of treatment (6 to 12 months). The secondary outcome was the mean per cent changes in BMD at the same sites with the full period of recommendation (18 to 24 months). A random-effects model was used to estimate the standardised mean differences (SMDs) and the 95% CIs. RESULTS:Seven studies, with 747 patients, were included. With the optimal period, the concomitant combination therapy demonstrated a significant advantage over a monotherapy in BMD improvement at the total hip (SMD 0.42; 95%?CI 0.26 to 0.58) and the femoral neck (SMD 0.30; 95%?CI 0.14 to 0.46), but not for the spine BMD (SMD 0.13; 95%?CI -0.17 to 0.43). With the full period, the concomitant combination therapy did not improve the BMD at the lumbar spine (SMD -0.06; 95%?CI -0.71 to 0.59), the total hip (SMD 0.05; 95%?CI -0.71 to 0.82) and the femoral neck (SMD -0.32; 95%?CI -1.15 to 0.50). CONCLUSIONS:Compared with anabolic monotherapy, the concomitant combination therapy of anabolic agents and bisphosphonates significantly improved the BMD at the total hip and femoral neck with a shorter term (6 to 12 months) and produced similar benefits on BMD for the longer term (18 to 24 months). Also, the effect of concomitant combination therapy might be affected by the dose of anabolic agents. PROSPERO REGISTRATION NUMBER:CRD42016041335.

SUBMITTER: Lou S

PROVIDER: S-EPMC5855398 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Combination therapy of anabolic agents and bisphosphonates on bone mineral density in patients with osteoporosis: a meta-analysis of randomised controlled trials.

Lou Shenghan S Lv Houchen H Li Zhirui Z Zhang Licheng L Tang Peifu P

BMJ open 20180301 3

<h4>Objective</h4>We aimed to determine whether the concomitant combination therapy of anabolic agents and bisphosphonates produces more effects on bone mineral density (BMD) than anabolic agents alone in patients with osteoporosis.<h4>Methods</h4>We searched MEDLINE, EMBASE and the Cochrane Library for publications from 1 January 1980 to 1 August 2016 to identify all the randomised controlled trials (RCTs) and quasi-RCTs. The primary outcome was the mean per cent changes in BMD at the lumbar sp ...[more]

PMID: 29500198

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Project description:Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Project description:ABSTRACT Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long‐term fracture risk. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen‐containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta‐analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%–5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%–3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%–2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%–6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%–5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%–5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N‐telopeptide (−52.2%, 95% CI −60.3% to −44.2%, p < 0.00001, n = 3 studies) and bone‐specific alkaline phosphatase (−34.2%, 95% CI −42.6% to −25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta‐analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This systematic review and meta‐analysis of randomized controlled trials demonstrates that nitrogen‐containing bisphosphonates improve bone density and lower bone turnover markers in early menopausal women (i.e. perimenopausal or <5 year postmenopausal), warranting further investigation of these agents for osteoporosis prevention.

Project description:BackgroundOsteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density.MethodsIn this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies.FindingsWe identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density.InterpretationTwo gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.

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Combination therapy of anabolic agents and bisphosphonates on bone mineral density in patients with osteoporosis: a meta-analysis of randomised controlled trials.

Publications

Combination therapy of anabolic agents and bisphosphonates on bone mineral density in patients with osteoporosis: a meta-analysis of randomised controlled trials.

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