Clinical Settings of Disorders of Bone in AIDS
It is important to emphasise that today in 2007 there are well over 40 million people world wide who are infected with the AIDS virus; and according to infor- mation given recently at an international televised meeting (Clinton Foundation) over 5 million more people are still infected annually. A high proportion of these are children. Many AIDS patients live in circumstances which do not enable them to receive the care and treatment outlined below; though greater international ef- forts in this direction are now being made.
Manifestations of AIDS Osteopathy
Many of the problems experienced by patients with AIDS (Acquired Immune Defi- ciency Syndrome) require hematologic, immunologic and osteologic investigations.
These problems include: cytopenias, lymphomas, infections, fever of unknown or- igin (FUO), hemorrhages, bone pain, and pathologic fractures. It is essential to emphasise that osteopathy in AIDS is an important, highly complex complication which has so far received too little attention. Hematologic disorders and neopla- sias have been extensively described and are well recognised, but not osteological problems. Since the latest treatments for AIDS now achieve longer survival times, it is all the more important to pay attention to the quality of life for which mobility and therefore skeletal integrity are crucial, particularly for the millions of children in- volved, because many of the more than 40 million people with AIDS are young.
Drugs used to treat AIDS may also be harmful to the bones; as is the decreased physical activity of many patients. In one study, evaluation of aspirates and bone marrow biopsies (n=120) frequently demonstrated dysplastic/aplastic changes in hematopoiesis, as well as inflammatory reactions in the stroma of the bone mar- row. The bone itself also regularly exhibited changes designated as “AIDS-Osteopa- thy”. These changes are summarised as follows:
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Reduced bone density (osteopenia – osteoporosis)
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Increased osteoclastic activity (secondary HPT)
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Disturbances in mineralisation (osteomalacia)
CHAPTER 11AIDS Osteopathy
124 Chapter 11 AIDS Osteopathy
Recent studies on the interaction of the AIDS infection and bone have postu- lated that the constant stimulation of T cells leads to activation of osteoclasts and thereby increased resorption via osteoprotegerin. In addition to the direct viral and drug-induced damage to bone cells, marrow cells and stroma, as well as the anomalies of vitamin D metabolism, many other secondary risk factors are also involved (Table 11.1). Recent international studies of bone density by DXA measure- ments in AIDS patients have now confirmed the frequent occurrence of osteopenia/
osteoporosis and pathological fractures, and in some cases even of osteonecrosis, as shown in a large study of patients from 1999 to 2002. The causes of the osteopathies in AIDS are very complex (as noted above) and are also influenced by the various therapies the patients have received. These in turn effect the clinical, biochemical and radiological manifestations. Moreover, fractures in AIDS patients have a very strong influence on quality of life, by the additional suffering and incapacity, the added requirements for care and nursing, the effect on mortality, as well as con- tributing greatly to the cost of treating the patients.
Diagnosis
Consequently all AIDS patients should undergo an osteological evaluation at time of diagnosis, including the following if at all possible:
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X ray of the lumbar spine in two planes
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DXA of lumbar spine and hip (annual monitoring)
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Examination of peripheral blood for calcium, phosphate, alkaline phosphatase, crosslaps, PTH, Vitamin D, TSH and testosterone/estrogen
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Complete blood count (CBC)
Results of clinical trials published in 2005 have now been summarised and sug- gestions as to screening and treatment have been made.
Table 11.1 Etiology of AIDS osteopathy Basic disorder
Hemopoietic cell defect?
T-cell activation
Bone marrow inflammation
Malnutrition
Gastrointestinal infections Immobilisation
Lipodystrophy Testosterone deficiency Vitamin D deficiency Infections
Hyperparathyroidism
Glucocorticoids Antibiotics Protease-Inhibitors
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When appropriate indications are present (cytopenias, atypical cells in blood films etc), and possibly (unclarified) osteopathies, a bone biopsy and aspirate should be obtained for clarification and diagnosis. It should be stressed that in AIDS the disorders of the bones of young people and adults begin in childhood – even in the neonatal and perinatal periods, therefore appropriate management of the pediatric patient is crucial.
Treatment Strategies
All AIDS patients would benefit from implementation of the guidelines given un- der “Basic Therapy of Osteoporosis” which include physical activity (physiother- apy if possible), bone-preserving life-style, adequate nutrition and supplements of calcium and Vitamin D. However should there already be osteoporosis at diag- nosis (T<–2.5 SD) or if the density measurements decrease in spite of the basic therapy (as above), then addition of an oral aminobisphosphonate is indicated. If difficulties arise with the oral route, then an aminobisphosphonate can be given i.v. which also forestalls problems of compliance and uncertainty as to whether or not the medication has been taken. The schedule is the same as previously noted:
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Alendronate 70 mg orally weekly
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Risedronate 35 mg orally weekly
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Ibandronate 3 mg i.v. every 3 months
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Zoledronate 5 mg i.v. annually
When osteomalacia and secondary hyperparathyroidism dominate the clinical picture, the daily supplement of Vitamin D can be increased to 3000 IU; alterna- tively an active metabolite of Vitamin D can be substituted. Serum calcium must of course be monitored.
To summarise, every second AIDS patient develops some form of osteopathy during the course of the disease. This can be a combination of osteoporosis, os- teomalacia and secondary hyperparathyroidism and frequently entails difficult clinical situations involving pathological fractures and bone pain. Studies are in progress to clarify to what extent the viral infection itself and/or the anti-viral therapy are/is responsible for the loss of bone mass. Secondary infections and li- podystrophy also add to the “osteoporomalacia”. If the diagnostic investigations (as described above) are applied and the basic therapy implemented, then AIDS osteopathy can be diagnosed and prevented in its early stages and even success- fully treated in the later ones. Studies have already been published on the efficacy of alendronate plus calcium and Vitamin D on bone mineral density – however, most of the patients were male with an average length of 8 years HIV infec- tion. Results of additional studies are pending.
Treatment Strategies
