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Unexplained low bone mineral density in HIV patients

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The risk of fragility fractures is increased among people living with HIV, according to research. Aidsmap reports that this increased risk couldn’t entirely be explained by reductions in bone mineral density suggesting a wider effect of HIV and its treatment on bone health. Overall, the authors believe their findings should lead to changes in guidelines for the monitoring, diagnosis and treatment of bone deficiencies in people with HIV. “We recommend acknowledging HIV and antiretroviral therapy (ART) as established risk factors for osteoporosis,” they write.

Dr Jakob Starup-Linde and his colleagues at Aarhus University Hospital in Denmark wanted to establish a clear understanding of bone health in people with HIV, including fracture risk, changes in BMD and treatment strategies. They therefore conducted a meta-analysis of published studies that looked at these issues, and also examined guidelines for the prevention, diagnosis, management and treatment of bone loss in people with HIV.

The report says their literature review included studies published up to June 2018. Randomised controlled trials and observational studies were eligible for inclusion, but only those reporting BMD results using dual-energy x-ray absorptiometry (DXA) of the hip and/or lumbar spine were included.

A total of 142 papers were included in the authors’ systematic review and 87 were eligible for inclusion in the meta-analysis. Starup-Linde and his co-authors believe their findings have implications for routine HIV care. They suggest that routine screening should be enhanced and that alendronate or zoledronate therapy to counter bone loss needs be started earlier, for instance if a person has a Z-score of -1.5.

“Besides anti-osteoporotic treatment, efforts should aim at environmental risk factors, such as smoking cessation, decreased alcohol intake, optimal nutritional intake, including increased physical activity and screening for risk factors for falls,” comment the authors. “We recommend optimisation of current guidelines with earlier initiation of osteoporosis prophylaxis and treatment.”

The report says the meta-analysis did not explore non-HIV related risk factors for bone problems. Another recent study, by researchers at Rigshospitalet, University of Copenhagen, examining data from 718 people living with HIV and 718 HIV-negative matched controls in Denmark, has done so. Of note, the researchers assessed bone mineral density using quantitative computed tomography rather than DXA, in other words a three-dimensional rather than two-dimensional scan.

Abstract 1
Objective: Osteoporosis is reported as a common comorbidity in patients living with HIV (PLHIV). The aim of this systematic review and meta-analysis is to assess the evidence on fracture risk in PLHIV, bone mineral density (BMD) in PLHIV compared with controls, longitudinal changes in BMD in PLHIV, and effect of antiosteoporosis treatment in PLHIV.
Methods: A systematic literature search was conducted using the databases Medline at PubMed and EMBASE using the search terms: “HIV” and “fracture” or “bone turnover,” or “bone mineral density.” Eligibility criteria followed the aim of the study and include randomized controlled trials and observational studies. Two reviewers extracted the data independently. Meta-analysis was performed using random-effects model assessing fracture risk, BMD compared with controls, and changes in BMD.

Results: One hundred forty-two of 2397 papers identified were included in the systematic review, and subsequently, 84 were included in the meta-analysis. The risks of a fragility fracture [1.51, 95% confidence interval (CI): 1.41 to 1.63] and hip fracture (4.05, 95% CI: 2.99 to 5.49) were increased. PLHIV have lower BMD at the hip (z-score −0.31, 95% CI: −0.46 to −0.27) and lumbar spine (z-score −0.36, 95% CI: −0.39 to −0.15) compared with controls. The reduced BMD did not fully explain the increased fracture risk in PLHIV.
Conclusions: Current management of osteoporosis in PLHIV follows general osteoporosis guidelines; however, the increased fracture risk is not fully explained by lower BMD, and thus, antiosteoporosis intervention may be beneficial at a higher BMD in PLHIV.

Authors
Starup-Linde, Jakob; Rosendahl, Simone Bruhn; Storgaard, Merete; Langdahl, Bente

Abstract 2
Background: Low bone mineral density (BMD) has been described in people living with HIV (PLWH). We examined the prevalence of low BMD measured by quantitative computed tomography (QCT), a method that allows 3-dimensional volumetric density measures at the thoracic spine, in well-treated PLWH and uninfected controls and assessed risk factors for reduced BMD.

Methods: Cross-sectional study including 718 PLWH from the Copenhagen Co-Morbidity in HIV infection (COCOMO) study and 718 uninfected controls matched on age and sex from the Copenhagen General Population Study (CGPS). Trabecular BMD was determined by QCT.
Results: Median BMD was 144.2 mg/cm3 in PLWH vs. 146.6 mg/cm3 in controls (P = 0.580). HIV status was not associated with BMD in univariable or multivariable linear analyses. However, a higher prevalence of very low BMD (T-score ≤ −2.5) was found in PLWH (17.2% vs. 11.0% in controls, P = 0.003). In unadjusted analysis, HIV was associated with very low BMD (odds ratio 1.68 [95% confidence interval: 1.24–2.27], P = 0.001), but this association was not significant after adjusting for age, sex, smoking, alcohol, body mass index, physical activity, and ethnicity. Previous AIDS-defining disease was associated with lower BMD, but no other associations with HIV-specific variables were identified.

Conclusion: Using QCT, we found a higher prevalence of very low BMD in PLWH than in controls. However, HIV status was not independently associated with BMD indicating that traditional risk factors contribute to the difference in prevalence of very low BMD. Focus on improvement of lifestyle factors, especially in PLWH with previous AIDS-defining disease, may prevent very low BMD in PLWH.

Authors
Thomsen, Magda T; Wiegandt, Yaffah L; Gelpi, Marco; Knudsen, Andreas D; Fuchs, Andreas; Sigvardsen, Per E; Kühl, Jørgen T; Nordestgaard, Børge; Køber, Lars; Lundgren, Jens; Hansen, Ann-Brit E; Kofoed, Klaus F; Jensen, Jens-Erik B; Nielsen, Susanne D

Full Aidsmap report

Journal of Acquired Immune Deficiency Syndrome abstract 1

Journal of Acquired Immune Deficiency Syndromes abstract 2

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