Risks for any fracture, fragility fracture, and hip fracture are increased in patients living with HIV (PLWHIV) compared with uninfected controls, but this heightened risk is not fully explained by reductions in bone mineral density (BMD), according to results of a systematic review and meta-analysis published in the Journal of Acquired Immune Deficiency Syndromes.
As the life expectancy of PLWHIV increases, medical issues commonly seen with older age are also becoming more common in this population. The goal of the current systematic review was to explore fracture risk and BMD changes in PLWHIV compared with uninfected control patients.
The researchers completed systematic literature searches in EMBASE and MEDLINE using PubMed. They included randomized controlled trials and observational studies. In assessing for quality, the investigators graded each study “for the level of evidence for prognostic studies or levels of evidence for therapeutic studies.”
A total of 2397 papers were found in the systematic review, of which 439 papers were assessed by full text for inclusion. The review included 55 papers on longitudinal BMD changes, 42 papers on fractures, 28 papers on BMD compared with control patients, 10 papers on anti-osteoporotic therapies, and 7 guidelines. Of these, 84 papers were included in the meta-analysis.
In a pooled analysis of 9 studies with a total of 64,633 PLWHIV and over 4.2 million control patients, the risk for any fracture was 53% greater in PLWHIV (relative risk [RR], 1.53; 95% CI, 1.46-1.61). In a similar fashion, there was a 51% increased risk (RR, 1.51; 95% CI, 1.41-1.63) for fragility fracture in PLWHIV compared with control patients. In a pooled analysis that included 9610 PLWHIV, there was a 4-fold increased risk for hip fracture (RR, 4.09; 95% CI, 3.03-5.52) compared with control patients.
A total of 28 papers included data on BMD at the hip and lumbar spine in PLWHIV compared with control patients, and 24 were included in the meta-analysis. In a pooled analysis of 3628 PLWHIV and 4108 control patients, BMD at the lumbar spine was significantly lower in PLWHIV (z score, -0.36; 95% CI, -0.46 to -0.27). BMD was also lower at the total hip in PLWHIV compared with control patients (z score, -0.31; 95% CI, -0.39 to -0.15). However, the researchers noted that this loss of BMD only explained a 15% increase in fragility fracture, indicating other deficiencies in bone health in PLWHIV that are not reflected in BMD.
There was a rapid decline in BMD at the lumbar spine and total hip after initiation of antiretroviral therapy (ART), which appeared to stabilize after 1 year. This BMD decrease was not more pronounced among users of tenofovir disoproxil fumarate (TDF). However, in sensitivity analyses of randomized controlled trials, abacavir and tenofovir alafenamide (TAF) were found to be superior to TDF in terms of preserving BMD.
“Treatment for 48 weeks with abacavir or TAF resulted in a clinically relevant reduction in bone loss compared with TDF,” the researchers wrote. “The differences in BMD at the spine and hip between patients treated with TAF and TDF continued to increase for up to 96 weeks and stayed stable for up to 144 weeks.”
The researchers noted several study limitations, including estimation of fracture risk based on populations that reported BMD, whereas studies reporting fracture risk did not include data on BMD results. Furthermore, no adjustment was made for potential confounders, including comorbidities, falls, medication use, lean mass, and lifestyle.
“[W]e recommend acknowledging HIV and ART as [established] risk factors for osteoporosis and therefore including [dual-energy x-ray absorptiometry] and information about bone-healthy lifestyle in the management of [PLWHIV]. In [PLWHIVs] aged 40 years or more with T-score at the spine or hip below -1.5, we suggest switching from TDF-containing ART to other regimens applicable to the patients. In addition, if other risk factors for fracture are present, speciﬁc osteoporosis prophylaxis should be initiated with zoledronate or alendronate,” wrote the researchers.
“New fracture predictors are needed in [PLWHIV], and BMD and bone microarchitecture should be investigated further,” they added.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Starup-Linde J, Rosendahl SB, Storgaard M, Langdahl B. Management of osteoporosis in patients living with HIV—a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2020;83(1):1-8.