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INTRODUCTION

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

INFECTION WITH the human immunodeficiency virus (HIV; abbreviations are listed in Table 1) or acquired immunodeficiency syndrome (AIDS) may have adverse effects on any organ system. Because there is no cure for HIV infection and because of ongoing new infection, the number of patients with HIV infection is still growing, especially in developing countries.(1) Moreover, the advent of highly active antiretroviral therapy in conjunction with improved standard antiviral and antibiotic regimens has dramatically changed the clinical course of HIV infection, resulting in prolonged survival in those with access to it.(1) As the population of HIV-infected individuals grows and ages, diseases of bone and mineral metabolism may become increasingly apparent, which may cause considerable mortality, morbidity, and impaired quality of life.

Table Table 1.. Glossary of Abbreviations
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In principle, the abnormalities of bone and mineral metabolism associated with HIV infection may be caused by direct interaction of HIV with cells of the bone and bone marrow microenvironment, chronic T cell activation, and abnormal cytokine production affecting osteoblast and osteoclast functions, disturbances of calcium homeostasis, parathyroid hormone (PTH) function, vitamin D metabolism, opportunistic or neoplatic diseases, and adverse effects of drugs.(2–4) To provide optimal health care for HIV-infected patients, early diagnosis and adequate treatment of HIV-associated disorders of bone and mineral metabolism are required. In this article, we review the spectrum of bone and mineral diseases in HIV infection and AIDS, discuss the mechanisms underlying their pathogenesis, and provide practical guidelines for prevention and treatment.

EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

Effects on osteoblastic lineage cells

Because of the high prevalence of hematological abnormalities in HIV-infected individuals such as anemia, thrombocytopenia, and leukopenia, it has been hypothesized that HIV may target pluripotent bone marrow-residing stromal cells and impair their proliferative capacity. Several studies have indicated clearly that latent persistent HIV infection of bone marrow stromal cells and subsequent alterations of the cytokine milieu may cause profound impairment of the bone marrow microenvironment, which may result in pancytopenia.(5–8) Direct adverse effects of HIV on preosteoblastic marrow stromal cells and on their differentiation toward the mature osteoblastic phenotype have not been observed. The ability of HIV to infect mature osteoblastic cells is still controversial. Although one study indicated that osteosarcoma cell lines (TE-85 and SaOS-2) when exposed to HIV revealed an infection rate of 1–5% of cells,(9) another study failed to confirm this.(10)

Infection of osteoblastic lineage cells may provide HIV with a nonlymphoid target and reservoir for latent infection and may directly explain abnormalities of bone formation in HIV-infected individuals. Moreover, it emphasizes the potential of HIV transmission through bone allografts.(11)

Effects on osteoclastic lineage cells

Direct effects of HIV on the differentiation or activation of osteoclasts have not been reported. However, persistent HIV infection or episodes of opportunistic infections have been shown to result in chronic T cell activation and a proinflammatory cytokine milieu.(12,13) Recent data suggest that activated T cells are capable of inducing functionally active osteoclasts by expressing both a cell-bound and a soluble form of receptor activator of nuclear factor (NF)-κB ligand (RANKL).(14,15) In the presence of permissive concentrations of macrophage colony-stimulating factor (M-CSF), RANKL is both necessary and sufficient to promote osteoclast formation and activation and to inhibit osteoclast apoptosis, thus expanding the pool of active osteoclasts.(16) Of note, RANKL gene expression is enhanced by cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α), which are elevated in HIV infection.(14,16) Moreover, IL-1 and TNF-α are capable of directly inducing differentiation and activation of osteoclasts in the absence of RANKL.(17,18)

Effects on biochemical markers of bone metabolism

Several studies have assessed biochemical markers of bone formation and resorption in patients with HIV(19–22) and their changes after therapeutic intervention.(21,22) Serrano et al.(19) reported lower serum concentrations of osteocalcin (a marker of bone formation) in 22 patients with HIV as compared with normal controls. Osteocalcin concentrations were lower in advanced stages of disease and were positively correlated with CD4+ lymphocyte counts.(19) Another small study reported a decrease of serum osteocalcin concentrations in 16 patients with HIV as compared with normal controls, especially after ongoing HIV infection of more than 2 years.(20) Serum levels of propeptide of type I collagen (PICP), another marker of bone formation, were found to be slightly lower in 13 patients with AIDS as compared with normal controls or patients with HIV infection.(21) Of note, treatment with recombinant human growth hormone (rhGH) significantly increased PICP levels in normal subjects and in patients with AIDS.(21)

In the largest analysis conducted to date, Aukrust et al.(22) evaluated bone markers and inflammatory cytokines in 73 HIV-infected patients. As HIV infection advanced, serum levels of osteocalcin decreased and those of C-telopeptide, a marker of bone resorption, increased. Serum levels of soluble TNF receptor (TNFR; a marker of inflammation) were correlated negatively with serum concentrations of osteocalcin and were correlated positively with serum levels of C-telopeptide.(22) After 24 months of therapy with highly active antiretroviral therapy, viral load decreased, the number of CD4+ lymphocytes increased, and serum levels of osteocalcin increased. Although there was no correlation between the serum concentrations of osteocalcin and C-telopeptide at baseline, both parameters were significantly correlated after treatment, indicating synchronization of bone remodeling once the virus load and inflammatory response are suppressed.(22)

Effects on bone histomorphometrical parameters

Data on histomorphometric analyses of bone remodeling in patients with HIV infection are sparse. Serrano et al.(19) assessed bone histomorphometry in 22 HIV-infected patients with normal bone mineral density (BMD). Surface-based bone formation rate, activation frequency, and osteoclast index were significantly lower in HIV-infected patients. Moreover, bone formation rate and activation frequency were lower in patients with advanced disease as compared with early disease and were correlated positively with the number of CD4+ T lymphocytes.(19)

Effects on BMD

Data on BMD in patients with HIV are limited. Using dual-energy X-ray absorptiometry, Paton et al.(23) reported a decreased BMD (−3%) at the lumbar spine in 45 HIV-infected men with a mean age of 36 years and different stages of the disease as compared with sex- and age-matched controls but no differences of total body or hip BMD. Serial measurements after a mean interval of 15 months revealed a slight decrease of 1.6% of total body BMD but no changes of spine or hip BMD. None of the patients had a T score < 2.5 at any time of the follow-up. Two smaller studies of 22 patients with a mean age of 28 years(19) and of 16 patients with an age range from 21 to 37 years(20) reported no differences between HIV-infected and normal individuals. However, because these studies assessed a small sample size and a population (young adults) at or around peak bone mass when the prevalence of osteoporosis is low, it is obvious that the magnitude of this problem is underestimated and that osteoporotic fractures will become more significant once this population of HIV-infected individuals ages. Two cases of severe osteoporosis in young African women with HIV infection may indicate a substantial change in the future epidemiology of osteoporosis in sub-Saharan Africa where HIV infection rates are as high as 30–40%.(24)

More recently, the use of a protease inhibitor has been identified as a risk factor of low bone mass.(25) In a study on 112 HIV-infected men, users of protease inhibitors had a 2.2-fold increased relative risk of osteopenia or osteoporosis as assessed by a whole-body BMD measurement.(25) Interestingly, these subjects also developed central obesity, which is considered to protect against bone loss, suggesting that the protease inhibitor had independent adverse effects on bone and fat tissue. Further studies using state-of-the-art bone densitometry techniques at various skeletal sites in larger numbers of HIV-infected patients are required to assess systematically BMD in HIV infection and to detect subtle abnormalities of BMD in this population.

Although measurement of BMD is not recommended as a routine test in HIV-infected patients, we recommend taking a detailed history to assess the personal risk for osteoporotic fractures and to perform a thorough clinical examination of the skeleton in every patient with HIV infection. Once additional risk factors of osteoporosis have been identified, assessment of biochemical markers of bone metabolism and measurement of BMD are recommended, especially in patients with overt hypogonadism and in those who are scheduled to receive a highly active antiretroviral therapeutic regimen that includes a protease inhibitor.

THE PTH SYSTEM IN HIV INFECTION

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

In HIV infection, the PTH system may be impaired through various mechanisms, including infectious or neoplastic etiologies,(26) impaired secretion of PTH at baseline and after provocation,(27–29) and PTH resistance.(30) Infiltration and destruction of the parathyroid glands has been reported in disseminated opportunistic infections with neck involvement, particularly with extrapulmonary Pneumocystis carinii or cytomegalovirus (CMV) disease.(26) Of note, parathyroid cells express receptors with structural similarity to the CD4 molecule, which acts as a cellular receptor for HIV and facilitates access of the virus to immune cells.(31) This mechanism may account for symptomatic hypoparathyroidism as the initial presentation of HIV infection when the virus load is high and the immune system is still intact.(32)

PTH serum levels were significantly lower in patients with HIV infection (n = 38; 13.9 ± 2.3 ng/liter) as compared with normal controls (n = 38; 38.1 ± 3.1 ng/liter).(28) Similar results were observed in 6 patients with AIDS (CD4+ count < 50/μl) who had PTH serum concentrations of 14 ± 2 ng/liter as compared with a normal population (n = 10; 23 ± 3 ng/liter) and patients with malignancies (n = 6; 35 ± 7 ng/liter).(29) After EDTA-induced hypocalcemia, patients with AIDS had a blunted PTH surge as compared with controls.(29) Of note, serum PTH levels were significantly lower in patients with AIDS (n = 23, 1.5 pmol/liter, range 0.2–4.3) as compared with patients with asymptomatic HIV infection (n = 20; 2.6 pmol/liter; range, 0.8-7.5), indicating that parathyroid impairment is a function of progression of HIV infection.(33) In the largest study on hypocalcemia in HIV infection to date, inappropriately low PTH secretion (despite hypocalcemia) accounted for as many as one-third of cases with hypocalcemia.(34)

In HIV-infected patients at any stage of the disease who present with tetany, muscle cramps, or electrocardiographic abnormalities, symptomatic hypoparathyroidism should be suspected, and serum concentrations of calcium, phosphate, and intact PTH should be assessed. If confirmed, rapid treatment consisting of a combination of calcium and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] should be initiated.(32)

CALCIUM HOMEOSTASIS IN HIV INFECTION

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

Hypercalcemia

Hypercalcemia has been confirmed in 2.9% of 66 patients with AIDS.(27) Hypercalcemia in HIV-infected individuals usually is of infectious, granulomatous, or neoplastic origin or a side effect of drugs (Table 2).(4,27) Infections associated with hypercalcemia in HIV-infected patients include opportunistic pathogens such as CMV,(35,36)Pneumocystis carinii,(37)Mycobacterium avium intracellulare,(38,39)Cryptococcus neoformans,(40,41) and Coccoides immitis.(41) Hypercalcemia in CMV disease is thought to result from direct osteoclastic activation by activated T cells or proinflammatory cytokines.(35,36) Carbone et al. reported a patient with AIDS-related hypercalcemia of unknown origin but with increased levels of TNF-α, IL-6, and IL-8, and serum calcium levels normalized after treatment with pamidronate.(42) Hypercalcemia in protozoal, fungal, and mycobacterial infection may result from extrarenal 1α-hydroxylation of 25-hydroxyvitamin D3 [25(OH)D3] by macrophages, monocytes, epithelioid cells, and multinucleated giant cells.(37–41) A similar mechanism has also been suggested in patients who present with AIDS-associated lymphoma and hypercalcemia.(43,44)

Table Table 2.. Abnormalities of Calcium Serum Levels in HIV Infection
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The use of rhGH for HIV-associated wasting was associated with a slight increase of serum concentrations of total calcium.(45) Possible mechanisms of rhGH-related hypercalcemia include increased intestinal calcium absorption through induction of calcium binding protein(46) and increased PTH secretion.(47) Sakoulas et al. reported a case of severe hypercalcemia following rhGH treatment in a patient with AIDS-related wasting and weight loss who required pamidronate therapy.(48) In this patient, PTH, PTH-related protein (PTHrP), and vitamin D levels were suppressed, indicating that alternative pathways caused hypercalcemia.(48) Hypercalcemia also has been reported in a patient treated with foscarnet for disseminated CMV infection.(49)

Severe hypercalcemia in HIV infection is managed by generous fluid replacement, use of calcium-lowering diuretics, and, in severe cases, treatment with a bisphosphonate. In any case, treatment of the underlying neoplastic or infectious disease and tapering the dose or discontinuation of drugs known to cause hypercalcemia is crucial.

Hypocalcemia

Overt, symptomatic hypocalcemia is uncommon in HIV-infected patients (Table 2), although subtle hypocalcemia has been detected in 6.5% of a total of 828 outpatients with HIV infection (compared with 1.1% of the normal population(34) and 17.9% of patients with AIDS (n = 66).(27) Among patients with HIV-related hypocalcemia, a subgroup analysis identified vitamin D deficiency in 48%, inappropriate PTH secretion despite hypocalcemia in 33%, overt hypoparathyroidism in 10%, and hypomagnesemia and secondary hyperparathyroidism in 4.8%, respectively.(34)

Severe hypocalcemia has been reported in HIV-infected patients after treatment with various drugs.(50) The most common agent associated with severe hypocalcemia in HIV infection is foscarnet, which is used to treat CMV infection.(51–53) Youle et al.(51) reported the occurrence of hypocalcemia after concurrent therapy with foscarnet and pentamidine for CMV infection in 4 patients, one of whom died with a serum calcium concentration of 1.4 mM (5.6 mg/dl). During foscarnet treatment for CMV retinitis in 13 patients with AIDS, 85–100% developed hypocalcemia(52,53) and 69% developed hypomagnesemia.(52) Foscarnet-induced hypocalcemia is caused by a combination of nephrotoxicity, resulting in renal wasting of calcium and magnesium,(52) and of complex formation of calcium with foscarnet (a phosphate analog), thus rapidly decreasing serum ionized calcium levels.(53) Hypocalcemia has also been reported in 10% of patients with AIDS receiving trimethoprim-sulfamethoxazole and in 15% receiving pentamidine for P. carinii pneumonia, respectively.(54,55)

From a clinical perspective, calcium and magnesium serum levels should be measured in all patients receiving these drugs. In addition, close monitoring of ionized calcium levels is mandatory during and shortly after foscarnet treatment.

VITAMIN D SYSTEM AND HIV INFECTION

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

Abnormalities of the vitamin D system

In HIV infection, decreased production and action of 1,25(OH)2D3 is the leading cause of hypocalcemia, accounting for 48% of cases.(34) Serum concentrations of 1,25(OH)2D3 were found to be markedly decreased despite normal levels of 25(OH)D3, to correlate positively with the severity of immunodeficiency and survival, and to drop to markedly low levels in patients with active infection with M. avium complex infection.(56,57) Detailed assessment of vitamin D metabolism in HIV-infected patients showed marked 1,25(OH)2D3 deficiency whereas serum concentrations of 25(OH)D3 and vitamin D binding protein were normal, suggesting impaired 1α-hydroxylation as its primary cause.(58) Of note, malabsorption, diarrhea, or weight loss were not correlated with 1,25(OH)2D3 levels, whereas phosphate levels were inversely correlated.(58) Advanced disease stage and increased serum levels of TNF-α were associated with 1,25(OH)2D3 deficiency, and increased TNF-α serum levels were most prevalent in patients with undetectable levels of 1,25(OH)2D3.(55) As suggested by Haug et al.,(58) lack of an increased 1α-hydroxylase activity in response to low 1,25(OH)2D3 levels may be caused by increased phosphate levels,(50) increased TNF-α levels,(59) partial PTH resistance,(2) and increased prolactin levels,(60) all of which may be present during HIV infection and may act in concert to reduce 1α-hydroxylase activity. As evident from in vitro studies, TNF-α may contribute to partial vitamin D deficiency by decreasing vitamin D receptors in osteoblastic lineage cells.(61) By contrast, enhanced 1,25(OH)2D3 synthesis is rare in HIV infection and usually is caused by excessive extrarenal 1α-hydroxylation.(37–39,43,44)

Modulation of the immune system

The immunomodulatory effects of vitamin D and its metabolites have long been appreciated.(62) 1,25(OH)2D3 modulates HIV expression and replication in monocytic cell lines, and has been found to either stimulate or inhibit it.(63–69) Because 1,25(OH)2D3 stimulates monocyte-to-macrophage maturation, its effect could be, at least in part, related to its regulation of cell differentiation. Alternatively, cytokines such as TNF-α released in response to 1,25(OH)2D3 could alter the susceptibility of immune cells toward the cytopathic effects of HIV.(70) Because of these ambiguous data and the potential stimulation of HIV replication by vitamin D and its metabolites in vitro—one study reported a 10,000-fold increase(65)—vitamin D supplementation or treatment is not recommended unless frank 1,25(OH)2D3 deficiency and concurrent hypocalcemia is present.

DIRECT INVOLVEMENT OF BONE

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

Skeletal complications resulting from direct involvement of bone by HIV-related infections or tumors are rare and generally reflect disseminated disease.(71) HIV-related osseous tumors usually represent non-Hodgkin's lymphoma or Kaposi's sarcoma (KS), and accounted for 16% and 4%, respectively, of HIV-infected patients who present with musculoskeletal abnormalities.(71) KS is the most frequent AIDS-related neoplasm with a prevalence of up to 20% in homosexual men.(72) At the time of skeletal manifestation, cutaneous, orofacial, pulmonary, and abdominal involvement of KS usually is present. KS may present as single or multiple osteolytic lesion(s). Less frequently, nonosteolytic disease may occur and can affect any bone site.(73–77) Osseous non-Hodgkin's lymphoma in HIV-infected individuals may be either primary(78–80) or secondary(81) and is usually a high-grade B cell lymphoma, although T cell lymphoma affecting bone have also been reported.(78) HIV-related osseous lymphoma usually presents as osteolytic lesions, and their propensity to cause hypercalcemia is related to their ability to express 1α-hydroxylase.(43,44) Of note, unusual tumors such as metastatic giant cell bone tumor (usually a benign and nonmetastatic disease(82) and nonsecretory multiple myeloma(83) may account for osteolytic bone disease in HIV infection.

Among HIV-related skeletal infections, a distinct spectrum of infectious agents has to be considered.(71) In an analysis of 45 HIV patients with musculoskeletal abnormalities, bacillary angiomatosis (caused by infection with Rochalimaea henselae or Rochalimaea quintana) accounted for 16% of musculoskeletal abnormalities.(71) Because of its cutaneous signs and symptoms and osteolytic lesions, bacillary angiomatosis has been termed a “pseudoneoplastic” infection and must be distinguished from KS.(84–87) Other infectious agents with skeletal tropism in HIV-infected patients include Mycobacterium haemophilum,(88)Aspergillus species,(89)Treponema pallidum,(90) and Acanthamoeba species.(91)

A high index of clinical suspicion, knowledge of the distinct etiology, rapid and straight-forward diagnosis, including early bone biopsy, and appropriate treatment are crucial in the management of bone involvement by HIV-related infections and neoplasms.

HYPOGONADISM IN HIV INFECTION

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

Sex hormone deficiency is a risk factor of osteoporosis in women and men.(13, 92–94) Bone loss associated with sex hormone deficiency is mediated through direct osteoblastic and osteoclastic effects, modulation of the cytokine milieu, and extraskeletal effects on calcium homeostasis. Replacement with sex steroid hormones, at least in part, can prevent these abnormalities.(13,92–94) Sex hormone deficiency is among the most frequent endocrine abnormalities in HIV-infected men, and its clinical symptoms (impotence and decreased libido) have been reported in 33% and 67%, respectively, of 70 patients with AIDS evaluated in an outpatient clinic.(95) Sex hormone deficiency in HIV-infected men is multifactorial and may be caused by hypothalamic and pituitary failure, direct gonadal destruction by HIV-related opportunistic infections or neoplasms, Leydig cell dysfunction induced by abnormal cytokine production, adverse effects of drugs (ketoconazole, ganciclovir, and chemotherapeutic agents), or the chronic and consumptive nature of HIV infection (fever, chronic stress, weight loss, and malnutrition).(96–98) Both gonadal and adrenal steroids have been shown to decline with progression of HIV infection and are correlated positively with lymphocyte counts.(95,99–102)

Neither the contribution of hypogonadism on bone metabolism nor the effect of hormone replacement therapy on bone metabolism and immune function have been assessed systematically in HIV-infected patients. Safe sex education is crucial before initiating hormone replacement therapy to prevent HIV transmission, once libido and sexual potency have been reestablished.

CONCLUSIONS

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES

Patients with HIV infection or AIDS may display various abnormalities of bone and mineral metabolism. Chronic viral infection, altered immune function, abnormal cytokine production, opportunistic infections, HIV-related neoplasms, and drugs are the major causes of bone and mineral disturbances in HIV-infected individuals (Table 3). Bone formation is decreased, bone resorption is normal or increased, and BMD generally is normal but may be decreased in users of protease inhibitors. Hypercalcemia and hypocalcemia are multifactorial in origin and usually caused by infections, neoplasms, or drugs. Hormonal changes in HIV infection include suppressed PTH secretion, impaired synthesis and action of 1,25(OH)2D3, and development of hypogonadism, all of which become most pronounced in advanced stages of HIV infection. A high index of clinical suspicion, early recognition, rapid establishment of the diagnosis, appropriate treatment, and correction of the underlying pathology are crucial in the management of patients suffering from HIV-associated abnormalities of bone and mineral metabolism.

Table Table 3.. HIV-Related Abnormalities of Bone Metabolism
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REFERENCES

  1. Top of page
  2. INTRODUCTION
  3. EFFECTS OF HIV INFECTION ON THE BONE AND BONE MARROW MICROENVIRONMENT
  4. THE PTH SYSTEM IN HIV INFECTION
  5. CALCIUM HOMEOSTASIS IN HIV INFECTION
  6. VITAMIN D SYSTEM AND HIV INFECTION
  7. DIRECT INVOLVEMENT OF BONE
  8. HYPOGONADISM IN HIV INFECTION
  9. CONCLUSIONS
  10. Acknowledgements
  11. REFERENCES
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