The Buzz: Dem Bones—Reports
of Abnormal Changes in HIV
by Daniel S. Berger, MD
Body habitus and metabolic
abnormalities in HIV- infection continue to get great press
and headlines—and they should. The alterations in fat redistribution
are sometimes gruesome and include various combinations of
manifestations, including posterior neck fat pads (buffalo
hump), increasing visceral fat (abdominal paunch), loss of
fat from extremities, face and buttocks, and increasing breast
mass. If one is bored of reading repeated reports of metabolic
problems that emphasize insulin resistance and diabetes as
well as elevations in cholesterol and triglycerides (and don’t
forget the elevations of lactic acid in the blood, a byproduct
of biochemical pathways occurring as tissues deprived of oxygen),
there is something new to contemplate. Bone mineral loss has
been emerging as a new metabolic concern in patients who are
HIV infected. Several reports of HIV-positive HAART (regimen)
treated patients with bone disorders have come to the surface.
One such disease of bone that results in death of bone tissue
due to circulation problems is called avascular necrosis.
The second reported disorder is osteopenia, or bone thinning
that may result in spontaneous bone fractures.
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The bony skeleton is an integral
part of the human anatomy. Besides the obvious characteristics
of movement and support, bone is dynamic, constantly turning
over with bone formation and resorption (bone remodeling).
Bone also acts as a mineral reservoir, and regulates calcium
and phosphate metabolism. When bone is being resorped, calcium
is extracted and the bone matrix is destroyed. Conversely,
bone formation requires normal levels of calcium, phosphate
and vitamin D. Various hormones (calcitonin and parathormone)
and several organs (kidney, intestine and brain) are also
involved in this process. Up to 15% of our total bone mass
turns over each year. A peak in bone mass occurs between ages
20 and 30 years. Equal rates of formation and resorption continue
to maintain stable bone mass until near 50 years of age. Thereafter
resorption increases over formation and bone density decreases
slowly. Certain diseases and certain medications can disrupt
this process and results in a loss of bone mass. As of recent,
HIV or HIV-negative related therapy is now being called into
question as a possible cause for increased bone turnover and/or
bone disorders.
Various reports of bone abnormalities
being observed began recently. Several studies have been presented
at international conferences and in medical journals. One
such meeting, the Second International Workshop on Adverse
Reactions and Lipodystrophy in HIV, met last fall in Toronto.
While the meeting primarily discussed the research relating
to fat redistribution, and its associated metabolic complications,
several reports of bone demineralization and related bone
disorders were presented. Researchers from Washington University
School of Medicine presented evidence of elevated bone turnover
and an additional study evaluated evidence of the inhibition
(stopping) of conversion by protease inhibitors of vitamin
D to the more active form [1,25(OH)2 vitamin D3], which is
needed for bone formation. Additionally, Dr. David Nolan from
the Western Australia HIV cohort showed higher rates of osteopenia
(bone thinning) and osteoporosis (increased bone softening
and loss of bone tissue) in individuals on protease inhibitors.
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In the area of avascular necrosis
(death of bone tissue associated with circulation problems),
a small group of 14 patients with this disorder was found
to have the association of previous Pneumocystis carinii
pneumonia infection, prior corticosteroid use (not anabolic
steroid use) and low CD4 T-cells (less than 50).
Lastly, Dr. Pablo Tebas recently
published a report in AIDS (2000;14:F63-F67) of a study
of 112 patients: 64 received protease inhibitors, 36 HIV-positive
patients were not exposed to protease inhibitors and 22 HIV
negative persons were used as controls. Various tests were
performed to assess bone density, including a specialized
x-ray scan (DEXA) to detect bone density reduction. The results
of the study showed that 50% of the patients from the group
of protease inhibitors use had lower bone mineral density.
This was compared with the 6% of the HIV negative controls
and 11% of the other HIV-positive patients with no prior protease
inhibitor use who showed reduced bone density. While the rates
of bone disorders reported here are shocking, one should question
how the patients were selected for the study. Most HIV treatment
clinics have not witnessed bone disorders this high, but do
not routinely test for bone density.
Presently and for patients
who are on antiviral therapy, there is no cause for alarm.
There is no evidence to suggest a need for changing one’s
antiviral therapy or regimen. Although there are increasing
numbers of patients being reported with bone disorders, most
HIV treaters are not observing these complications at these
alarming numbers. Also, a cause and effect relationship to
antiviral therapy has not been demonstrated, nor do we know
of any mechanism for which protease inhibitors can cause bone
mineral loss or turn over.
Moreover other causes and
factors are associated with bone loss. Avascular necrosis
is associated with alcohol abuse, hyperlipidemia (elevated
cholesterol and triglycerides), sickle cell disease, systemic
lupus erythematosis and the use of anabolic steroids and testosterone.
Osteopenia (bone loss) has been associated with prolonged
bed rest, severe weight loss, disorders of the parathyroid
and thyroid hormone axis as well as medications that include
corticosteroids, pentamidine, phenobarbital and ketoconazole.
Thus one must take into account these other factors when examining
the rates of bone disorders, as well as individual patients.
Thus far, it is not indicated
to routinely check for bone densities in HIV-positive patients
on treatment. However, if signs or symptoms occur that suggest
the possibility of a bone disorder, such as bone pain, which
means weakness in a particular bone structure, then appropriate
X-rays, MRIs and bone density testing should be done. To be
proactive, weight bearing exercises and calcium supplements
can be considered, but should be discussed with one’s physician.
Lastly, a relatively new class of drugs called biphosphonates
reduce bone resorption and are being increasingly used for
certain bone thinning diseases, such as osteoporosis.
There is much that needs
to be examined to improve our understanding of this relatively
new reported complication of HIV. Large controlled studies
should be undertaken to better explore the risks of bone loss
in HIV-related disease in our patients, as well as studying
HIV negative controls on antiviral therapy. Other work should
look into the etiology (cause) and possible relationship to
various antiviral agents.
Daniel S. Berger, M.D. is Medical
Director for NorthStar Medical Center, Clinical Assistant
Professor of Medicine at the University of Illinois at Chicago
and editor of AIDS
Infosource (www.aidsinfosource.com).
He also serves as medical consultant and columnist for Positively
Aware.
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