Bone health and HIV

HIV Australia | Vol. 11 No. 2 | July 2013

HILA HASKELBERG outlines a range of bone-related health conditions, discussing proactive steps HIV-positive people can take to maintain optimal bone health.

Since the introduction of highly active antiretroviral therapy in 1996, the quality of life and survival of HIV-positive people has improved dramatically. In developed countries, HIV infection has evolved into a chronic disease.

Yet, as the age of people living with HIV increases, new challenges are emerging including the occurrence of several non-AIDS conditions associated with ageing.

These include bone loss, or low bone mineral density (BMD)¹ and higher rates of fractures² seen in people living with HIV when compared with those without HIV. Different factors may play a role in the relationship between bone, HIV and antiretroviral therapy.

By being aware of these issues and taking a range of proactive steps, people with HIV can help to maintain optimal bone health.

Bone tissue

Bone is a metabolically active tissue that constantly renews itself throughout life, in a process called remodelling (reconstruction). The tissue is mainly made of collagen and minerals. Collagen is a protein that gives the bone its flexible structure, and minerals, such as calcium and phosphorus, add strength.

Different hormones participate in the regulation of remodelling, such as calcitonin, parathyroid hormone, oestrogen, and testosterone. In addition, vitamin D is important for maintenance of calcium and phosphate levels in the blood.

During remodelling, old bone is removed (bone resorption) and new bone is placed (bone formation). Until the third decade of life, there is a higher rate of bone formation than bone resorption.

After the peak bone mass has been reached, BMD usually declines over time as the balance between bone formation and bone resorption changes.

Bone formation and resorption remain synchronised throughout life; this balance is affected by a variety of genetic, environmental and pathological factors.

Some of the factors that have been associated with bone loss are age and sex, ethnicity, physical activity and immobility, smoking, alcohol consumption, anti-osteoporotic drugs, corticosteroids and antiretroviral drugs.³

Deficiency in vitamin D, as well as decreased calcium intake and impaired intestinal absorption of calcium, can also result in weakening of the bones.⁴

Osteoporosis and HIV

Skeletal status is most commonly assessed by measuring BMD using dual energy X-ray absorptiometry (DXA). This is a painless and relatively quick test that uses a type of X-ray to assess the level of minerals in the bones.

The World Health Organization (WHO) separates reduced BMD into two categories: osteoporosis, defined as a BMD at least 2.5 standard deviations below normal peak values for sex-matched young adults (i.e., a T-score less than -2.5) and osteopenia, defined as a T-score between -1 and -2.5.⁵

People with osteopenia are at greater risk of possibly developing osteoporosis over time and therefore should have a DXA scan done every two to five years to monitor their bones status.

There has been extensive research into bone diseases in people without HIV, mainly in postmenopausal women as the hormonal changes during menopause lead to bone loss.

In HIV-positive individuals, a range of skeletal disorders has been described including osteopenia, osteoporosis⁶ ⁷ ⁸osteomalacia (softening of the bones), and osteonecrosis (death of bone tissue due to reduced blood supply).

Osteoporosis is the most common bone disease in Australia.⁹ It results from excessive bone loss leading to weakening of the bones. In many cases, osteoporosis remains undiagnosed until a fracture occurs, most commonly at the spine, hip or forearm.

In population studies comparing the incidence of fracture rates among people with and without HIV, fractures rates have been found to be significantly higher among HIV-positive people.¹⁰ ¹¹

Bone mineral density, HIV and antiretrovirals

The mechanisms underlying the possible relationship between BMD, fractures and HIV are not fully understood and may involve effects of both HIV and antiretroviral therapy, in addition to traditional risk factors.

Some of the traditional risk factors tend to be more common in HIV-positive people and include smaller body size, low vitamin D levels, smoking, alcohol use and co-infection with hepatitis C.

The chronic inflammation associated with untreated HIV infection can also affect the balance between bone resorption and formation and lead to bone loss.¹²

The role of antiretroviral therapy in bone loss is yet to be determined. Different studies show that initiation of antiretroviral therapy is associated with a short-term decrease in BMD in the first year of 2 to 6%, after which time the BMD tends to stabilise.¹³ ¹⁴

Looking at specific antiretroviral drugs, therapy with tenofovir¹⁵ ¹⁶¹⁷ and some protease-inhibitor-based regimens¹⁸ have been associated with bone loss, though the mechanism involved is unknown.

Clinical management

BMD measurement is used to determine whether to start osteoporosis treatment and to monitor the treatment efficacy.¹⁹

Recently published guidelines by McComsey et al., for the management of bone disease in HIVpositive adults recommend performing a DXA scan for patients with fragility fractures, for all HIV-positive postmenopausal women and for HIVpositive men aged 50 years or older.²⁰

The guidelines also highlight the importance of identifying secondary causes of osteoporosis, for example hypogonadism, vitamin D deficiency, or liver disease.

A 10-year fracture risk can be estimated using the WHO Fracture Risk Assessment Tool (FRAX) (www.shef.ac.uk/FRAX), which has been validated for adults aged over 40 years.

McComsey et al., recommend that if the risk of all osteoporotic fracture is >20% or the risk of hip fracture is >3%, then the initiation of anti-osteoporotic medications should be considered.²¹

There are different types of drugs that are used to treat osteoporosis: bisphosphonates (which lower the rate of bone resorption), hormone therapy, and drugs that stimulate bone formation.

There are a few studies that have investigated the short term effects of these drugs on BMD in HIV-positive people;²² the effects found were similar to the people without HIV.

There are some preventative steps that can be taken for good bone health. These include balanced nutrition consisting of adequate sources of calcium, vitamin D, and phosphorus.

Vitamin D is also produced in the body during an exposure to sunlight. If there is a concern that the levels of calcium or vitamin D are still low, the person should discuss with their treating physician if supplements are required.

Weight-bearing activities and resistance exercises can help strengthen the skeleton as well.

Other preventative measures for good bone health are suggested under the ‘bone health’ section of the AFAO website: www.yourbodyblueprint.org.au

References

1 Brown, T., Qaqish, R. (2006). Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS, 20(17), 2165–2174.

2 Triant, V., Brown T., Lee, H., Grinspoon, S. (2008). Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. Journal of Clinical Endocrinology and Metabolism, 93(9), 3499–3504.

3 Haskelberg, H., Carr, A., Emery, S. (2011). Bone Turnover Markers in HIV Disease. AIDS Reviews, 13(4), 240–250.

4 Holick, M. (2007). Vitamin D deficiency. N Engl J Med, 357(8), 266–281.

5 Kanis, J., Melton, L., Christiansen, C., Johnston, C., Khaltaev, N. (1994). The diagnosis of osteoporosis. Journal of Bone and Mineral Research, 9(8), 1137–1141.

6 Brown, T., et al., (2006), op. cit.

7 Y in, M., Zhang, C., McMahon, D., Ferris, D., Irani, D., Colon, I., et al. (2012). Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. Journal of Clinical Endocrinology and Metabolism, 97(2), 554–562.

8 Carr, A., Miller, J., Eisman, J., Cooper, D. (2001). Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight preantiretroviral therapy. AIDS, 15(6), 703.

9 Henry, M., Pasco, J, Nicholson, G, Kotowicz, M. (2011). Prevalence of osteoporosis in Australian men and women: Geelong Osteoporosis Study. Medical journal of Australia, 195(6), 321–322.

10 Triant, V., et al., (2008), op. cit.

11 Güerri-Fernandez, R., Vestergaard, P., Carbonell, C., Knobel, H., Avilés, F., Soria Castro, A., et al. (2013). HIV infection is strongly associated with hip fracture risk, independently of age, gender and co-morbidities: A population-based cohort study. Journal of Bone and Mineral Research.

12 Ofotokun, I., McIntosh, E., Weitzmann, M. (2012). HIV: inflammation and bone. Current HIV/AIDS Reports, 9(1), 16–25.

13 Gallant, J., Staszewski, S., Pozniak, A., DeJesus, E., Suleiman, J., Miller, M., et al. (2004). Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA, 292(2), 191.

14 Martin, A., Bloch, M., Amin, J., Baker, D., Cooper, D., Emery, S., et al. (2009). Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir- Lamivudine: a randomized, 96-week trial. Clinical Infectious Diseases, 49(10), 1591.

15 Gallant, J., et al., (2004), op. cit.

16 Bedimo, R., Maalouf, N., Zhang, S., Drechsler, H., Tebas, P. (2012). Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS, 26(7), 825.

17 McComsey, G., Kitch, D., Daar, E., Tierney, C., Jahed, N., Tebas, P., et al. (2011). Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS clinical trials group A5224s, a substudy of ACTG A5202. J Infect Dis, 203(12), 1791–1801.

18 Duvivier, C., Kolta, S., Assoumou, L., Ghosn, J., Rozenberg, S., Murphy, R., et al. (2009). Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS, 23(7), 817–824.

19 International Society for Clinical Densitometry. (2007). Official Positions. Retrieved from: http://www.iscd.org

20 McComsey, G., Tebas, P., Shane, E., Yin, M., Overton, E., Huang, J., et al.(2010). Bone Disease in HIV Infection: A Practical Review and Recommendations for HIV Care Providers. Clinical Infectious Diseases, 51(8), 937–946. 21 ibid.

22 Mondy, K., Powderly, W., Claxton, S., Yarasheski, K., Royal, M., Stoneman, J., et al. (2005). Alendronate, vitamin D, and calcium for the treatment of osteopenia/ osteoporosis associated with HIV infection. Journal of Acquired Immune Deficiency Syndromes, 38(4), 426–431.

Hila Haskelberg is a PhD candidate and Clinical Project Coordinator at the Kirby Institute, The University of NSW.