Treatment Overview

The principal aim of treatment for osteoporosis is to reduce the incidence of fractures. Treatment should help the patient maintain mobility, avoid falls, correct nutritional deficiencies and provide pain relief. In people living with HIV (PLWHIV), treatment with bone protective therapy should be considered in those with osteoporosis who have experienced a fracture or have a high probability of fracture after exclusion of secondary causes of osteoporosis.1



Guidelines

The European AIDS Clinical Society (EACS) Guidelines specifically provides recommendations for treating osteoporosis in PLWHIV,2 The Department of Health & Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents lists osteoporosis as a metabolic complication of antiretroviral (ARV) therapy and states that no change is needed in recommendations regarding ARV therapy or monitoring.3 



The EACS recommend the following:2

  • decrease falls by addressing falls risks
  • ensure sufficient dietary calcium (1–1.2 g daily) and vitamin D (800–2000 IU daily) intake
  • refer to national/regional guidelines on treatment of osteoporosis
  • if no guidelines available, consider bisphosphonate treatment in all osteoporotic postmenopausal women and men >50 years old and those with a history of fragility fracture, with either:
    • alendronate 70 mg once weekly per os (PO)
    • risedronate 35 mg once weekly PO
    • ibandronate 150 mg oral monthly or 3 mg intravenously (IV) every 3 months
    • zoledronate 5 mg IV once yearly
       
  • use bisphosphonate with calcium and vitamin D replacement
  • no significant interactions between bisphosphonates and ARVs
  • if on tenofovir, consider renal bone disease
  • in complicated osteoporotic cases (e.g. young men, premenopausal women, recurrent fracture despite bone protective therapy), refer to endocrinologist
  • if osteoporotic and on bisphosphonate treatment, repeat dual energy x-ray absorptiometry (DXA) after 2 years


Find out about Non-HIV-specific treatment guidelines
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Pharmacological treatment of osteoporosis1

Bisphosphonates are first-line therapy for osteoporosis and are the only agents that have been assessed in an HIV-positive population.4–6



Table 1. Drugs available to treat osteoporosis.1,4–6


First-line therapy Comment on use
Bisphosphonates Alendronate and zoledronate have shown effects on BMD in 48-week, randomised controlled trials in PLWHIV4-6
 
Second-line therapy  
Estrogen-replacement therapy Effective for postmenopausal women, although des carry a risk of cancer, cardiovascular disease and deep-vein thrombosis
Raloxifene (a selective estrogen-receptor modulator) Does not increase the risk of breast cancer in postmenopausal women
Intranasal calcitonin Has a relatively low efficacy compared with bisphosphonates
Teriparatide (an analogue of parathyroid hormone) Should be reserved for patients with severe osteoporosis and those who have already been treated with bisphosphonates (should not be used concomitantly)

There is currently no evidence to suggest that switching ARV regimens improves BMD and reduces fracture risk. 
 



Treatment of vitamin D deficiency

The EACS Guidelines recommend that vitamin D replacement be administered to individuals with a deficiency:

  • 800–2000 IU daily can be provided according to national recommendations and/or availability of preparations (oral and parenteral formulations)
  • aim to increase serum 25-(OH) vitamin D by >50 nmol/L and maintain serum parathyroid hormone levels within normal range
  • combine with calcium where there is insufficient dietary calcium intake
     

The Institute of Medicine of The National Academies suggest a dietary intake of vitamin D of 600 IU daily in males and females aged 1–70 years, and 800 IU daily in those aged >70 years.7 The recommended dietary intake of calcium is 1000 mg daily in adults aged ≤50 years, and then 1200 mg daily in females aged 51–70 years and 1000 mg daily in males in the same age range. All adults aged >70 years require an intake of 1200 mg calcium daily.



Although the rationale for vitamin D supplementation is clear, it should be noted that there are few data available to support these recommendations. Additionally, there is thought to be substantial variation in the target range of vitamin D concentrations, including seasonal differences.8 There is also little evidence to support a correlation between vitamin D supplementation and decreased fracture risk.





References

  1. 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.
  2. European AIDS Clinical Society (EACS). Guidelines. Version 8.2. Accessed 19 April 2017.
  3. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Accessed 21 February 2011.
  4. Rozenberg S, Lanoy E, Bentata M, et al, and ANRS 120 Fosivir Study Group. Effect of alendronate on HIV-associated osteoporosis: a randomized, double-blind, placebo-controlled, 96-week trial (ANRS 120). AIDS Res Hum Retroviruses. 2012 Sep;28(9):972-80. 
  5. Pinzone MR, Moreno S, Cacopardo B, Nunnari G. Is there enough evidence to use bisphosphonates in HIV-infected patients? A systematic review and meta-analysis. AIDS Rev. 2014 Oct-Dec;16(4):213-22.
  6. Raffi F, Orkin C, Clarke A, et al. Long-term (96-week) efficacy and safety after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in HIV-infected, virologically suppressed adults. J Acquir Immune Defic Syndr. 2017 Mar 6. [Epub ahead of print]
  7. IOM (Institute of Medicine). 2011. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press. Accessed 24 April 2017.
  8. Kull M Jr, Kallikorm R, Tamm A, Lember M. Seasonal variance of 25-(OH) vitamin D in the general population of Estonia, a Northern European country. BMC Public Health. 2009;9:22.