UK studies on bone health: increasedfracture rates reported in HIV-positive people
Simon Collins, HIV i-Base
Several studies reported on various aspects of HIV and bone health.
Barry Peters and colleagues from Kings College London reported results from a cross-sectional case-control study looking at fracture risk, bone mineral density (in lumbar spine and hip) and a wide panel of bone-related investigations.
Cases were 223 randomly selected HIV-positive patients stratified by age with age and gender matched controls. Investigations included serum calcium, phosphate, 25OH vitamin D, alkaline phosphatase, parathyroid hormone, albumin, sex hormone binding globulin (SHBG), testosterone, CD4, HIV RNA. Fracture risks (fracture history, smoking, alcohol, BMI, activity level etc) were included to calculate FRAX score and remaining lifetime fracture probability (RLFP).
The study included patients with broad demographics: 133(60%) were male, 106(48%) were Caucasian, 71(33%) had AIDS at diagnosis.
Osteoporosis/osteopenia were present in 13%/39% of males and 11%/29% females, and was approximately 2.4/3.0 fold greater than age-matched controls. The overall mean 10-year fracture risk was 3.16%. RLFP exceeded 1.0 in 76% HIV patients, and <20% controls.
Factors associated with low BMD after multivariate analysis included having started antiretroviral therapy (adjusted OR 3.61; 1.38,9.42, p 0.01); BMI (aOR 0.90; 95%CI 0.83,0.96, p<0.001); alkaline phosphatase (aOR 1.01; 1.00,1.02, p<0.05) and testosterone (aOR 1.04; 1.01,1.07, p<0.01).
No association was found between fracture risk and age, gender, ethnicity CD4 count or vitamin D levels.
A second UK cross-sectional study reported fracture risks from 859/1050 HIV-positive patients attending the Lawson HIV clinic at Brighton Hospital who returned detailed questionnaires (that included demographics, lifestyle and fracture and HIV history and risk). This cohort was less diverse: 775 were men and 84 women; 87% Caucasian, with mean age was 43 years (range 19-77 years) and mean duration of HIV infection of 8 years (range 023 years).
Overall, 125 (15%) subjects reported 200 fractures: 119 (15%) men and 6 (7%) women. Common fracture sites were forearm (n=65), tibia/fibula (n=29), hand/foot (n=22) and digit (n=19). Hip fractures occurred in 6 subjects and 2 had clinical vertebral fractures.
Fractures significantly grouped in either younger (75% less than 25 years, median 7-12) or older (17% were 4060 years). In the older group, typical osteoporotic fractures sites included forearm (n=6, mean age 48 years) and tibia/fibula (n=4, mean age 49 years); there was 1 hip fracture (age 46 years).
Both studies commented on management and monitoring with the first suggesting the higher fracture risk supports screening at an earlier age compared to HIV-negative populations and the Brighton study suggesting that screening may be important in younger patients.
Significantly higher rates of osteopenia and osteoporosis in HIV-positive compared to age- and sex-matched HIV-negative people have been well documented for at least 12 years, and this is now supported by more recent studies reporting increased fracture rates. 
Paediatric and adolescent HIV infection will compound these risks by reducing bone development (which peaks at around 30 years, subsequently declining). Additionally, reduced bone mineral density is one of the few negative associations with HIV treatment. 
Some clinics already recommend baseline DEXA scans for people older than 50 years. Paediatric guidelines have yet to directly address the long-term impact of both HIV and antiretroviral treatment on bone health, other than in the context of tenofovir treatment. Longer duration of both HIV infection and use of HIV treatment during the period of bone growth (up to age 30) would support a caution for optimising bone health and monitoring in
- Peters B et al. Fracture risk in HIV and the need for guidelines: the Probono-1 trial. 10th International Congress on Drug Therapy in HIV Infection. 711 November 2010, Glasgow. Abstract P099. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):O50doi:10.1186/1758-2652-13-S4-P099. http://www.jiasociety.org/content/13/S4/P99
- Samarawickrama A et al. Rates of bone fractures in a cohort of HIV-infected adults in the UK. 10th International Congress on Drug Therapy in HIV Infection. 711 November 2010, Glasgow. Poster abstract P100. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):P100doi:10.1186/1758-2652-13-S4-P100. http://www.jiasociety.org/content/13/S4/P100
- See report in April HTB from 17th CROI 2010. https://i-base.info/htb/10254
- Grund B et al. Continuous antiretroviral therapy decreases bone mineral density. AIDS. 2009 July 31; 23(12): 15191529. doi: 10.1097/QAD.0b013e32832c1792. Free online acces: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748675/