Causes

Bone remodeling – which involves bone resorption and bone formation, and which is under the control of two cell types (osteoblasts and osteoclasts) – is essential for maintaining a healthy skeleton. Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue resulting from impaired bone remodeling. 



Figure 1. Loss of architecture in osteoporotic bone

Images reproduced with permission from http://www.iofbonehealth.org and http://courses.washington.edu/bonephys.

In the general population, causes of osteoporosis and fragility fractures include:1


  • failure to develop a strong skeleton
    • genetics – limited growth or abnormal bone composition
    • nutrition – calcium, phosphorous and vitamin D deficiency, poor nutrition
    • lifestyle – e.g. lack of weight-bearing exercise, smoking, excess alcohol intake
  • loss of bone due to excessive resorption
    • decreased sex hormone production
    • calcium and vitamin D deficiency
    • increased parathyroid hormone
    • excessive production of local resorbing factors
  • failure to replace lost bone due to impaired formation
    • loss of ability to replenish bone cells with age
    • loss of local growth factors
    • decreased production of systemic growth factors
  • increased tendency to fall
    • loss of muscle strength
    • slow reflexes and poor vision
    • drugs that impair balance

       

Causes in people living with HIV (PLWHIV)

Osteopenia and osteoporosis are more prevalent among PLWHIV than those without HIV. However, the underlying mechanisms are not well understood and are probably multifactorial, with likely contributions from HIV infection, antiretroviral (ARV) therapy and traditional risk factors.

HIV

  • in vitro, HIV proteins have been shown to increase osteoclast activity2 and decrease bone formation by promoting osteoblast apoptosis3
  • the proinflammatory cytokines tumour necrosis factor (TNF) and interleukin-6 (IL-6) have been found to be constitutionally produced in increased amounts in chronic HIV infection, and may contribute to osteoclast activation and resorption4

Treatment

  • Initiation of ARV is associated with a reduction in bone mineral density (BMD) of 2–6% regardless of the choice of agent5
    • while differences may exist between drugs, this has not yet been clearly determined and mechanisms through which ARV drugs may exert their effect on BMD have not yet been elucidated6
    • 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 BMD7 

Although ART initiation is associated with loss of BMD, it is unclear whether any effect might be cumulative with a number of therapies, or if continued ART use affects BMD over the long-term.




 

References

  1. US Department of Health and Human Services. Bone Health and Osteoporosis: A report of the Surgeon General. Chapter 2. The basics of bone in health and disease.  Accessed 4 January 2007.
  2. Nacher M, Serrano S, González A, et al. Osteoblasts in HIV-infected patients: HIV-1 infection and cell function. AIDS. 2001;15:2239-2243.
  3. Fakruddin JM, Laurence J. HIV-1 Vpr enhances production of receptor of activated NF-kappaB ligand (RANKL) via potentiation of glucocorticoid receptor activity. Arch Virol. 2005;150:67–78.
  4. Thomas J and Doherty SM. HIV infection – a risk factor for osteoporosis. J Acquir Immune Defic Syndr. 2003;33:281-291.
  5. Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodelling: emerging insights into the pathophysiology of osteoporosis. N Engl J Med. 1995;332:305-311. 
  6. 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. 
  7. Mallon PW. HIV and bone mineral density. Curr Opin Infect Dis. 2010;23:1–8.