Osteoporosis

Key considerations for people living with HIV

Osteoporosis describes a condition where bone strength (including bone mass and bone quality) is compromised. Osteoporosis increases the risk of fractures, even as a result of minimal trauma and fracture risk is particularly elevated in elderly individuals. Identification and treatment of osteoporosis in older people is an important primary means of fracture prevention. However, for the majority of people, osteoporosis is asymptomatic until a fracture occurs.



Osteoporotic fractures are a major cause of morbidity and mortality, and have a heavy economic burden. Importantly, fractures can be avoided with early detection of the condition and appropriate treatment.

Osteomalacia (softening of bones) can also occur in people living with HIV (PLWHIV), although its prevalence and causes are not well understood.

Osteomalacia may be accompanied by low bone mineral density (BMD) and is characterized by impaired mineralization of the bone matrix that causes bones to soften, most often caused by severe vitamin D deficiency. 



When describing conditions that weaken the bone, the International Society of Clinical Densitometry recommends the terms ‘low bone mass’ or ‘low bone density’, although the term ‘osteopenia’ is still considered acceptable.¹ When patients have chronically reduced bone density (see Diagnostic tools for definitions), typically associated with a risk or history of fragility fractures, the term ‘osteoporosis’ is commonly used.²

Epidemiology

Osteoporosis is the most common bone disease in the general population and the majority of cases occur in postmenopausal women. There are multiple factors associated with the development of osteoporosis; major risk factors (often referred to as ‘classic’ risk factors) are increasing age, female sex, low body mass index (BMI), corticosteroid or alcohol excess, and smoking. The lifetime risk for a wrist, hip or vertebral fracture is estimated to be around 30–40% in developed countries.³  

• The prevalence of osteoporosis in PLWHIV appears to be greater than in the general population;⁴ 10–15% of people living with HIV are estimated to have osteoporosis, with a further 60% thought to have osteopenia.⁵ These conditions are particularly prevalent among post-menopausal women⁵ and those with a low body weight⁶
• In addition, fracture prevalence in HIV-infected men and women is increased compared with non-HIV-infected individuals;^7–9 however adequately powered studies examining risk factors in PLWHIV are lacking.
• As the HIV-infected population ages, osteoporosis and fractures are likely to become a growing problem in PLWHIV (in populations of relatively young adults).
   

Pathophysiology

The causes of low BMD in PLWHIV appear to be multifactorial, and include HIV infection, ARV therapy, tobacco or narcotic use, and vitamin D deficiency.¹⁰

• HIV infection is associated with increased bone turnover, reflected in higher markers of bone formation and bone resorption in PLWHIV, compared with non-HIV infected individuals.¹⁰
• Initiation of antiretroviral therapy is associated with a significant (2–6%) but discreet loss of BMD, the majority of which occurs within 48–96 weeks after the initiation of therapy, although BMD appears to be relatively stable in patients receiving established ART.¹⁰
• Although loss of BMD has been observed with initiation of any antiretroviral regimen that has been studied to date, greater losses have been observed in those prescribed NRTIs (such as  tenofovir) and some PIs.¹⁰
• Initiation of antiretroviral therapy is associated with increases in bone turnover, as measured by increases in markers of both bone formation and bone resorption.¹¹
• Increases in markers of bone resorption occur early after antiretroviral initiation, coincident with the greatest declines in BMD, with increases in markers of bone formation following later after ART initiation, possibly as a compensatory measure that limits further loss of BMD.¹¹ 


   

Treatment

The main aim of treatment is to reduce the incidence of fractures. It is still not known if pharmacological interventions for low BMD in PLWHIV (especially younger PLWHIV) will reduce the risk of fracture. Although most guidelines for the treatment of osteoporosis do not refer specifically to PLWHIV, the European AIDS Clinical Society (EACS) Guidelines provides guidance on management of osteoporosis in PLWHIV and recommendations have also been published. These guidelines and recommendations suggest identifying those patients at greatest risk of low BMD, measuring BMD in those at risk and treating osteoporosis where identified.⁵ Its main recommendations are to follow national guidelines when available; otherwise, bisphosphonate therapy with vitamin D and calcium supplementation should be considered.⁵

References

1. International Society of Clinical Densitometry. Official Positions. 2007. 
2. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Accessed 26 May 2011.
3. WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level. Summary Meeting Report, Brussels, Belgium, 5–7 May 2004. Accessed 21 February 2011.
4. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006;20:2165–74.
5. European AIDS Clinical Society (EACS). Guidelines. Version 6.0. Accessed 4 July 2012. 
6. Bolland MJ, Grey AB, Gamble GD, Reid IR. Low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis. J Clin Endocrinol Metab. 2007;92:4522–4528. 
7. Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large US healthcare system. J Clin Endocrinol Metab. 2008;93:3499–3504. 
8. Womack JA, Goulet JL, Gibert C, et al. Increased risk of fragility fractures among HIV-infected compared to -uninfected male veterans. PLoS One. 2011;6:e17217. 
9. Young B, Dao CN, Buchacz K, et al. Increased rates of bone fracture among HIV-infected persons in the HIV outpatient study (HOPS) compared with the US general population, 2000–2006. Clin Infect Dis. 2011;52(8):1061–1068.
10. McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51:937–946. 
11. Mallon, P. HIV and bone mineral density. Curr Opin Infect Dis. 2010;23(1):1–8.