Transcript Related Guidelines

Treatment of Reduced BMD in HIV

Ana Milinkovic, MD, PhD · Chelsea and Westminster Hospital


November 16, 2020

This transcript has been edited for clarity.

Why should we focus on the bone health in people living with HIV (human immunodeficiency virus)? Because we know that some people living with HIV are more likely to have incident fractures and because we know that mortality and morbidity increase in all age groups 12 months after a fracture—especially a hip fracture. A fracture can lead to increased difficulty in completing essential activities for 60% of individuals and increased restriction in all other activities for up to 80% of individuals.[1]

People living with HIV have traditional risk factors for fragility fractures, which can be modifiable or nonmodifiable. Nonmodifiable risk factors are increasing age: the risk of hip fracture doubles every 5 to 7 years. Previous fragility fractures are also one of the risk factors, as are female sex, wide duration margin, family history (a key factor), and reduced lifetime exposure to estrogen. Modifiable risk factors are those that we can do something about. They include low bone mineral density, drug use (for example, corticosteroids, which lead to a decreased bone formation), low body mass, hypogonadism in men, smoking, excessive alcohol use, a diet low in calcium, vitamin D deficiency, poor visual acuity, and risk of falls, as well as long-term immobilization.

The presence of traditional risk factors in people living with HIV is high. Vitamin D deficiency is common and has been related to the use of some of antiretrovirals.[2] In most of the cohorts, around 40% of people living with HIV are smokers. Heavy alcohol use is common, both in people living with HIV and the general population, and recreational drug use is relatively common.[3] Cocaine use and injection drug use are associated with a greater risk of incident fracture. Further research is needed to understand whether the risk of fracture is related to the increased rate of falls associated with recreational drug use alone, which would be something that everybody would expect, or direct effects on bone metabolism as well.[4]

Although primary risk factors are more common, secondary causes such as HIV and antiretroviral therapy could tip the balance of the bone homeostasis of bone formation and accelerate bone resorption. HIV is associated with high prevalence of low bone mineral density, high rate of fractures, and overall high rate of comorbidities—some of which have been related to an increased risk of falls and bone loss. 

The impact of the choice of antiretroviral treatment on bone has been extensively studied. We know that TDF (tenofovir) exposure is associated with increased risk of bone fracture, as shown in the EuroSIDA Study.[5] But we also know that long-term concomitant exposure to both TDF and boosted PIs (protease inhibitors) is associated with greater osteoporotic fracture rates than exposure to either TDF alone or boosted PIs alone.[5] For all these reasons, it is important for assessment of fracture risk to be performed systematically in people living with HIV. 

There are many ways to decrease the risk of fracture in people living with HIV. First of all, we need to aim to decrease falls by addressing the fall risk. We need to ensure that sufficient dietary calcium and vitamin D intake are provided daily to our patients. 

Where appropriate, screen for osteoporosis and refer to the national guidelines for treatment of osteoporosis. If there are no guidelines available, consider use of bisphosphonates. When you are using bisphosphonates, you need to think about repeating a DXA (dual-energy X-ray absorptiometry) scan every 2 years afterward and reassessing the need for continued treatment for up to 3 to 5 years.[6] 

What are the best algorithms for diagnosis, prevention, and management of bone fragility in people living with HIV? Most countries have their own algorithms. The UK has an algorithm for diagnosis and prevention. But if your country does not have one, one of the best algorithms that we sometimes use is the Position Statement from the Swiss Association against Osteoporosis.[]

When you are thinking about the use of calcium and vitamin D, especially calcium, think about the interactions of a fully balanced cocktail, such as magnesium, iron, and calcium, with integrase inhibitors, targeting drug–drug interactions, and decide what’s the best combination of drugs to be used. 

When you are managing bone loss in people living with HIV, you need to think about the most likely etiology. Is it the antiretroviral treatment? Is it related to HIV? Or is it related to traditional risk factors such as age? In some patients, it could be all of these.

Therefore, when you are considering ways to adequately manage low bone mineral density in patients living with HIV, an individualized approach to treatment, in addition to lifestyle modifications, should be considered. One possibility is the use of calcium, vitamin D, bisphosphonates, or all of these in combination with a switch to a different antiretroviral agent. When you switch away from the TDF containing the protease inhibitor boost–containing regimen, choose the best treatment option, think about drug–drug interactions, and review all concurrent medications.

It is very important to apply adequate practice to manage bone disease. Effective HIV management improves prevention and treatment of comorbidities. Closing the morbidity and mortality gap between people living with HIV and the general population should be our aim. Therefore, we need to create an approach that must be built on an individualized management plan focused on prevention of disability. 


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