Human Immunodeficiency Virus Infection and Hip and Knee Arthroplasty.

BACKGROUND: Modern management of human immunodeficiency virus (HIV) infection has afforded patients longevity while increasing the burden of arthroplasty procedures because of the increased risk of osteonecrosis, fragility fractures, and degenerative joint disease. Early publications on hip and knee arthroplasty in HIV-positive patients reported a high risk of complications, although some more recent publications demonstrated acceptable outcomes. Despite the widespread nature of the HIV pandemic, there is a paucity of literature addressing outcomes following joint arthroplasty in infected patients. We pooled available studies to obtain the best evidence regarding the safety of total hip and knee arthroplasty procedures in HIV-positive patients. The studies identified were heterogeneous, precluding a meta-analysis. However, we performed a review of the literature focusing on complications and outcomes. METHODS: Twenty-one published English-language articles involving 6,516,186 joints were identified by a systematic review as suitable for inclusion in the study. The articles were analyzed for complication and prosthesis survivorship rates and relative risks. RESULTS: An overall complication rate of 3.3% was found across the 19 articles that provided such data. HIV-positive patients had a significantly elevated risk of periprosthetic joint infection, at 7.6%, compared with HIV-negative patients, at 3.3% (relative risk = 2.28, 95% confidence interval = 2.14 to 2.43). Eleven articles were suitable for analysis of prosthesis survivorship, and survivorship rates did not differ significantly between HIV-positive and negative patients. CONCLUSIONS: Total hip and total knee arthroplasty appear to be safe procedures with acceptable outcomes in HIV-positive patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort.

BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

A case of dengue-related osteonecrosis of the maxillary dentoalveolar bone.

Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with non-surgical management.

Methotrexate-related lymphoproliferative disorder arising in the gingiva of a patient with rheumatoid arthritis.

Methotrexate (MTX) is the primary drug used in the management of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. MTX is a strong immunosuppressive agent and has been reported to cause iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPDs). Stomatitis caused by MTX-related cytotoxicity may occur, but gingival MTX-related LPDs are rare. In this article we present a case of gingival MTX-related LPD in a 60-year-old male with RA. The local findings of the gingival ulceration and alveolar bone exposure were similar to those of bisphosphonate-related osteonecrosis of the jaw. However, he had never received bisphosphonate therapy. The biopsy specimen of the gingival lesion was diagnosed as diffuse large B-cell lymphoma with Epstein-Barr virus positivity. Immediate withdrawal of MTX resulted in marked remission of the LPD.

Mandibular osteonecrosis and Ramsay Hunt syndrome following a case of herpes zoster.

Varicella zoster virus (VZV) is the agent that causes chicken pox, a common childhood infection that characteristically presents as vesicular rashes affecting the trunk and head. After the primary infection has resolved, VZV lies dormant in the spinal dorsal root ganglia or extramedullary cranial nerve ganglia until reactivation results in herpes zoster (shingles). The sensory nerves of the trunk, as in classic shingles, and the fifth cranial nerve, as in trigeminal zoster, are the most frequently affected. Shingles is an acute viral infection characterized by the appearance of painful unilateral vesicular rash usually restricted to a dermatomal distribution of a sensory nerve. The rash of shingles is usually preceded by pain and paresthesia. A rare, severe complication of the reactivation of VZV in the geniculate ganglion of the facial nerve is Ramsay Hunt syndrome (RHS). RHS is characterized by otalgia, vesicles in the auditory canal, and ipsilateral facial paralysis. An even rarer complication of VZV infection includes post-zoster osteonecrosis. This report documents a case of severe mandibular osteonecrosis and RHS after an outbreak of herpes zoster and treatment strategies.

Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms.

OBJECTIVE: To explore the correlation between post-severe acute respiratory symptom (SARS) patients with osteonecrosis, investigate the etiology of post-SARS osteonecrosis and select the sensitive molecular symbols for early diagnosis and distinguish the high-risk population. METHODS: The studied subjects were divided into two groups. Sixty-two post-SARS patients with osteonecrosis were one group, and 52 age- and sex-matched healthy people were as normal controlled group. Empty stomach blood samples from cubital veins were collected from both groups. Plasminogen activator inhibitor (PAI) by means of enzyme-linked immunosorbent assay and PAI-1 4G/5G polymorphism was detected by polymerase chain reaction and solid phase oligonucleotide assay. RESULTS: The blood agents of post-SARS patients changed obviously with 15.64 ± 13.85 U/ml while the control group 7.96 ± 4.27 U/ml; 4G/4G genotype for the PAI-1 polymorphism detected in post-SARS group was more than that of the control group, but had no statistical significance. The plasma PAI activity was related to homozygote 4G/4G genotype. This reveals that homozygote 4G/4G genotype may be a susceptible gene mark to Chinese osteonecrosis patients. CONCLUSION: Plasminogen activator inhibitor-1 is sensitive blood symbol for screening high-risk susceptible population; 4G/4G PAI-1 genotype may be an etiological factor in osteonecrosis.

Outcomes of cementless primary THA for osteonecrosis in HIV-infected patients.

BACKGROUND: Symptomatic osteonecrosis of the joint is a frequent debilitating complication in patients who have been infected with the human immunodeficiency virus (HIV). In earlier reports, outcomes of primary total joint arthroplasty in such patients have been poor due to early failures, high infection rates, and increased complication rates. We report on the clinical and radiographic outcomes of primary total hip arthroplasty (THA) in nonhemophilic, HIV-infected patients as compared with the outcomes in a cohort of osteonecrosis patients who did not have this disease. METHODS: Thirty-four HIV-infected patients (forty-four hips) who underwent primary THA for the treatment of osteonecrosis during the period of 2001 through 2008 were compared with a control cohort of seventy patients (seventy-eight hips) who also underwent THA for the treatment of osteonecrosis but did not have HIV or other high-risk factors for revision. The patients in the HIV study group (eleven women and twenty-three men) had a mean age of forty-eight years (range, thirty-four to eighty years) and were followed for a mean of seven years (range, four to eleven years). Evaluated outcomes included implant survivorship, Harris hip score, infection rate, activity score, postoperative Short-Form 36 (SF-36) health survey score, and radiographic outcome. RESULTS: Kaplan-Meier survival analysis demonstrated no significant difference in aseptic implant survivorship between the HIV and comparison cohorts at the five-year (100% vs. 98%, respectively) and ten-year (95% vs. 96.5%, respectively) follow-up times. In addition, at the time of final follow-up, the mean postoperative Harris hip scores (85 points in the HIV group vs. 87 points in the comparison group), activity scores (5.7 points in the HIV group vs. 6.1 points in the comparison group), and SF-36 physical (43 points in the HIV group versus 46 points in the comparison group) and mental component summary scores (54 points in the HIV group versus 57 points in the comparison group) were statistically similar between the two cohorts. There were two late infections in the HIV cohort as compared with none in the comparison cohort. CONCLUSIONS: Our results demonstrated excellent implant survivorship, clinical and radiographic outcomes, and minimal complications at the time of midterm follow-up in the HIV-infected patient group. We believe that the outcomes associated with primary THA are improving in this patient population as a result of better medical management; however, late infections are potential complications.

An unusual complication of tooth exfoliation and osteonecrosis following herpes zoster infection of trigeminal nerve: a case report and literature review.

Osteonecrosis following herpes zoster infection is a rare but severe complication, and clinicians' awareness is important for early detection and management of this condition. A case of herpes zoster of the left maxillary division of the trigeminal nerve is reported in a young female having no concurrent predisposing factors, with accompanying rare complications of alveolar bone necrosis and rapid tooth exfoliation. Acyclovir was used to manage the case effectively. The previously reported similar cases in the literature have been reviewed and the pathophysiology of tooth exfoliation and osteonecrosis by varicella zoster viruses is discussed.

Maxillary osteonecrosis and spontaneous teeth exfoliation following herpes zoster.

BACKGROUND: Reports of osteonecrosis and spontaneous tooth loss following herpes zoster infection of the fifth cranial are extremely rare. Only 39 previously recorded cases of post-zoster osteonecrosis have been found in the literature. The unusual feature of the case of interest to the dental surgeon is a rare complication of tooth exfoliation and maxillary osteonecrosis. CASE REPORT: This article reports a case of 52-year-old man with herpes zoster infection of the trigeminal nerve and related alveolar bone necrosis and teeth loss. The etiology and management of herpes zoster infection associated with destructive sequelae are discussed. DISCUSSION: Very few cases of osteonecrosis and spontaneous teeth exfoliation secondary to herpes zoster are found in the literature. The exact mechanism by which herpes zoster induces these destructive changes in the alveolar bone and teeth cannot be proposed. As Varicella zoster virus is an aneurotropic virus, the possible provoking factors may be the infection of the nerves innervating the periosteum or the chronic inflammatory changes in the form of adverse periodontal disease and delayed healing of the extraction sockets associated with compromised host resistance.

Unusual oral complications of herpes zoster infection: report of a case and review of literature.

A case of herpes zoster infection with unusual oral complications involving the mandibular division of the trigeminal nerve is presented. The post-herpetic complications of osteonecrosis, spontaneous exfoliation of teeth, and subsequent pathologic fracture of mandible in the absence of concurrent predisposing factors in a 65-year-old man are demonstrated. Forty-one cases with osteonecrosis and spontaneous exfoliation of teeth previously presented in the literature are reviewed. This is the first report of pathologic fracture after herpes zoster infection.

Osteonecrosis in patients after severe acute respiratory syndrome (SARS): possible role of anticardiolipin antibodies.

OBJECTIVES: This study examined the anticardiolipin antibodies in post-SARS (severe acute respiratory syndrome) osteonecrosis patients to investigate the etiology of post-SARS osteonecrosis, and to eventually provide valuable information for the early diagnosis of nontraumatic osteonecrosis and for the susceptible population screening. METHODS: This study recruited 62 post-SARS osteonecrosis patients and 52 age- and gender-matched healthy controls. Fasting blood samples were collected from all the subjects through cubital veins. Immunoglobulins A, G and M (IgA, G and M) types of anticardiolipin antibodies were examined by enzyme-linked immunosorbent assay. The routine examinations of prothrombin time, thrombin time, prothrombin activity, and international normalized ratio were also performed. RESULTS: There were 21 of 62 post-SARS osteonecrosis patients (33.9%) who showed at least one type of anticardiolipin antibodies. The titers of specific IgA, IgG, and IgM were 11.33 +/- 11.209 APL, 5.127 +/- 5.927 GPL, and 17.821 +/- 10.606 MPL, respectively. There were only 4 of 52 subjects in the control group (7.7%) who showed positive anticardiolipin antibody with titers of IgA at 10.702 +/- 3.126 APL, IgG at 5.184 +/- 4.780 GPL, and IgM at 14.684 +/- 5.516 MPL. There were significant differences between the 2 groups confirmed by t-Test and chi(2) test (P < 0.05), while no significant differences were observed in prothrombin time, thrombin time, prothrombin activity, and international normalized ratio results between the 2 groups. CONCLUSIONS: The incidences of anticardiolipin antibodies were increased in the post-SARS osteonecrosis patients and anticardiolipin antibodies may play a role in the pathogenesis of post-SARS osteonecrosis.

Thrombophilia in human immunodeficiency virus-infected patients with osteonecrosis: Is there a real connection? The first case-control study.

Several reports have described an increased incidence of osteonecrosis in human immunodeficiency virus-infected patients (HIV+), but the cause has not been established. The association between thrombophilia and osteonecrosis in HIV+ was studied. A case-control study in HIV+, 19 cases and 38 controls, was designed. Magnetic resonance imaging was made in both groups to confirm or exclude hip osteonecrosis. The extensive tests of thrombophilia were measured, and the clinical data were recorded, nadir of CD4(+) cell count and well-known risk factors for osteonecrosis. Thrombophilia has been frequently found both in patients with and without osteonecrosis (thrombophilia, 68.4% vs 60.5%), but no specific thrombophilia tests were significantly associated with osteonecrosis. A low nadir of CD4(+) (<60 cells/microL) and corticoid use were significantly (P < .05) associated with osteonecrosis. In multivariate analysis, only nadir of CD4(+) <60 cells/microL remained a predictor of osteonecrosis (odds ratio = 7.33; 95% confidence interval, 1.80-29.82, P = .005). Thrombophilia might have a limited role in the development of osteonecrosis in HIV+. Nadir of CD4(+) <60 cells/microL and corticoid use were main factors.

Prevention and management of trigeminal herpes zoster and postherpetic neuralgia.

Herpes zoster (HZ, also known as shingles) is caused by the reactivation of a dormant varicella zoster virus and can be a source of significant morbidity. Oral manifestations can include vesicular eruptions of the mucosa, osteonecrosis with tooth loss, and postherpetic neuralgia (PHN). This article discusses treatment for trigeminal nerve involvement with herpes zoster, as well as for the painful syndrome PHN.

Fracture healing in HIV-positive populations.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-alpha) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

[Avascular necrosis in a man with HIV infection]. / Avaskulaere knoglenekroser hos en patient med hiv-infektion.

Recently, a high incidence of avascular necrosis (AVN) has been reported in HIV-infected individuals. We present a further case of AVN of both femoral heads, the left distal femur and the proximal tibia in a 19-year-old HIV-positive man. The patient complained of severe pain in both hips, which had lasted 10 months. The diagnosis was aided by radiological assessment and radioisotope bone scan and confirmed by magnetic resonance imaging. The patient had been receiving antiretroviral therapy for 30 months and had no other known risk factors for developing AVN. We recommend early evaluation of musculoskeletal pain in HIV-infected patients to rule out AVN.

Changes in coagulation and fibrinolysis of post-SARS osteonecrosis in a Chinese population.

The purpose of this study was to detect changes in coagulation and fibrinolysis of post-severe acute respiratory syndrome (SARS) Chinese patients with osteonecrosis, investigate the aetiology of post-SARS osteonecrosis (ON), and select the sensitive molecular markers for identifying the susceptible population. For this study, blood samples were collected from 88 patients with post-SARS ON and 52 healthy people. Activated partial thromboplastin time (APTT), protein C (PC), antithrombin III (AT-III), plasminogen activator inhibitor (PAI), activated protein C resistance (APC-R), plasminogen (PLG), von Willebrand's factor(vWF), D-dimer (D-D), fibrinogen (Fib), and homocysteine (HCY) were examined by enzyme-linked immunosorbent assay (ELISA). We noted that blood agents of patients with ON changed obviously. APTT, PC, AT-III, PAI, APC-R, and PLG were significantly different between the two groups. Hypercoagulation and hypofibrinolysis were found in patients with post-SARS ON. Therefore, these examinations can be used to screen a population susceptible to ON. Measurements of APTT, PC, AT-III, PAI, APC-R, and PLG are sensitive blood tests for screening purposes.

Alveolar bone necrosis and tooth exfoliation following herpes zoster infection: a review of the literature and case report.

BACKGROUND: Herpes zoster (HZ) presents as a cutaneous vesicular eruption in the area innervated by the affected sensory nerve, usually associated with severe pain. Oral manifestations of HZ appear when the mandibular or maxillary divisions of the trigeminal nerve are affected. METHODS: This is a case report of a 63-year-old woman with HZ infection with trigeminal nerve involvement that led to a rapid loss of alveolar bone and exfoliation of two teeth. RESULTS: The initial intraoral examination showed redness of the alveolar mucosa and gingiva of the lower right quadrant with multiple well-delimited and painful erosive lesions affecting the attached gingiva around the teeth. Two weeks later, teeth number 27 (lower right canine) and 28 (lower right first premolar) had class III mobility, flow of purulent exudate from the gingival sulcus, and deep pockets (>11 mm). The radiological examination showed advanced alveolar bone loss around both teeth. The prognosis for teeth number 27 and 28 was considered hopeless, and they were extracted. Due to extensive necrosis there was no interdental alveolar bone. The case is presented with a review of clinical data from patients with trigeminal HZ infection associated with osteonecrosis or exfoliation of teeth previously reported in the literature. The mechanisms by which the HZ infection leads to the alveolar bone necrosis are discussed. CONCLUSIONS: Extensive osteonecrosis and exfoliation of teeth in the area innervated by the nerve affected by HZ has been reported after HZ infection. Clinicians should be aware of this possible outcome after a trigeminal HZ infection.

Avascular necrosis of bone in severe acute respiratory syndrome.

AIM: To report the incidence of avascular osteonecrosis (AVN) in severe acute respiratory syndrome (SARS) patients. MATERIALS AND METHODS: Sixty-seven SARS patients who had large joint pain between March 2003 and May 2003 underwent both plain radiographs and magnetic resonance imaging (MRI) examination on the same day. All patients received steroids and ribavirin treatment. All plain radiographs and MR images were analysed by two experienced musculoskeletal radiologists. Any abnormalities, location, extent, morphology, the number, size and signal intensity of lesions were evaluated. RESULTS: Twenty-eight patients were identified with AVN, The mean time to diagnosis of AVN was 119 days after the onset of SARS, or 116 days after steroid use. Three patients had early bilateral AVN of the femoral head, four patients of one femoral head, five patients of the bilateral hips and knees, four patients of the ipsilateral hip and knees, 10 patients of the knee(s), one patient of the right proximal fibula, and one patient of the knees and talus. Results of hip, knee and ankle plain radiographs were negative. CONCLUSION: AVN can occur in the patients with SARS. AVN had a strong association with steroid use. More studies are required to confirm whether the virus itself can also lead to AVN.