Anti-retroviral therapy
In those with low BMD or osteoporosis, tenofovir disoproxil fumarate should be avoided.35 A new formulation of tenofovir, tenofovir alafenamide (TAF) is associated with less bone and renal toxicity compared to TDF. In those at high risk of bone toxicity, TDF therapy should be changed to TAF.12,13,35 Studies examining switching from regimens containing TDF to TAF containing regimens have shown improvement in bone mineral density whilst being non-inferior in maintaining viral suppression.52,13Boosted protease inhibitors have been implicated in causing bone loss in some studies and should be avoided if possible in those with low bone density.6 Therapy with integrase inhibitors is associated with less bone loss.28
Diet and lifestyle
General recommendations include ensuring an adequate calcium and protein intake, cessation of cigarette smoking, avoiding excessive alcohol, maintaining a healthy body weight and ensuring an adequate but safe exposure to sunlight as a source of vitamin D.1 The Australian recommended dietary intake of calcium is 1300mg per day for women over 50, 1000mg per day for men 50-70 years and 1300mg per day for men over 70 years.14 Calcium should be obtained through dietary intake when able. At least three serves of dairy food per day is recommended.14 Regular exercise is also recommended, especially progressive resistance training either alone or combined with weight-bearing exercise.1,9 In those patients taking dolutegravir as part of their antiretroviral drug regimen, calcium supplements should be taken 6 hours before or 2 hours after the dose of dolutegravir as calcium may reduce the absorption of this agent.34
Vitamin D levels should be measured, and supplementary vitamin D should be given to those with vitamin D insufficiency (< 50 nmol/L) or deficiency (<25 nmol/L).9 A serum 25-hydroxy vitamin D level of > 50nmol/L should be maintained.1 Vitamin D replacement should be undertaken before bisphosphonate therapy is begun.
Pharmacological therapy
Agents used to treat osteoporosis in Australia include the bisphosphonates (alendronate, risedronate and zoledronic acid), denosumab (a therapeutic monoclonal antibody that neutralises RANKL) and teriparatide (a recombinant N-terminal portion of parathyroid hormone). Each agent is supported under the Pharmaceutical Benefits Scheme (PBS) with varying indications (Table 3).1 If a patient does not meet PBS criteria but has a calculated 10-year fracture risk of either 3% or greater at the hip or 20% or greater for a major osteoporotic fracture then non-PBS subsidised treatment should be considered and discussed with the patient.
Alendronate has been shown to be effective in increasing BMD in HIV-infected populations.17,20 Zoledronic acid has also been shown to be effective and a single dose of intravenous zoledronic acid prevents ART-induced bone loss in treatment-naïve HIV-infected patients.21 Zoledronic acid has been shown to be more effective in increasing BMD than switching TDF in HIV-positive adults with low bone mass.22 .
Denosumab (Prolia) is a commonly used osteoporosis medication with good fracture risk reduction data for post-menopausal females49. It is delivered as a subcutaneous injection every 6 months. There is no data on its efficacy in the HIV positive population. Its rapid offset of action means that it must be given every 6 months with delays or cessation resulting in losses of previous BMD gains50. Recent case studies have also suggested that during this period of rapid offset there is an increased risk of vertebral fractures51. Denosumab should not be used if the prescriber is not confident of patient compliance with the treatment regimen. Teriparatide (Forteo) is currently the only anabolic agent available in Australia for the treatment of osteoporosis. There are restrictive PBS prescription criteria for teriparatide including having a fracture after 12 months of anti-resorptive therapy. There is very little data on its use in the HIV positive population.
Unlike studies in the general population, no agent has been shown to decrease fractures in HIV-infected groups. In those who have responded well to therapy (T-score more than -2.5 and no recent fractures), treatment can be ceased after 5-10 years but restarted if further fractures are sustained, a significant drop in BMD occurs or if a new issue develops that increases fracture risk.1 Side-effects of bisphosphonate therapy include gastrointestinal irritation, medication-related osteonecrosis of the jaw and atypical fracture of the femur.1,23 Before and whilst taking bisphosphonates, dental review is recommended.1In cases of treatment failure or medication intolerance, referral to a specialist is indicated. HMG-CoA reductase inhibitors show a beneficial effect on BMD in HIV-infected adults on ART. Compared to placebo, patients receiving rosuvastatin modestly increased their BMD over 48 weeks. This change was significantly different to placebo.39
Table 3. Pharmaceutical Benefit Scheme indications for osteoporosis medications
|
Medication |
PBS Indication |
|
Alendronate, Risedronate, Denosumab |
1. Patient is aged 70 years or older and has a BMD T score of -2.5 or less or 2. Patient has had a minimal trauma fracture |
|
Zoledronic acid |
1. Patient is aged 70 years or older and has a BMD T score of -3 or less or 2. Patient has had a minimal trauma fracture |
|
Teriparatide |
1. Patient has had at least 2 minimal trauma fractures, with one new symptomatic fracture occurring after at least 12 months of anti-resorptive therapy, and patient has a BMD T-score of -3 or less |