Low Bone Mineral Density In Patients Research Articles

Possible Association of Combined Vitamin D Receptor and Estrogen Receptor Genotypes and Low Bone Mineral Density in Jordanian Postmenopausal Women

The genetics of osteoporosis has been extensively studied over the last 20 years. Many of the studies have been aimed at identifying possible risk factors and possible association with low bone mineral density (BMD). Vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphisms were the first to be studied. Some studies have shown a possible association for individual VDR and ER or combined VDR and ER genotypes in some populations, and others showed lack of such an association. This study is aiming at identification of a possible association with low BMD in Jordanian postmenopausal women. We used restriction fragment length polymorphisms (RFLPs) to study four polymorphisms in the VDR gene and two polymorphisms in the ER gene. Our sample was composed of 100 normal controls and 120 samples from patients with symptomatic vertebral fractures. The results showed a possible association of the ppxx genotype with low BMD in controls and patients and an association of the AaBbTT genotype with high BMD in control subjects. The AABBTT, AABBTTFF, and AABBTTFFPPXX genotypes showed a possible association with low BMD in patients. Further studies are needed to confirm the last finding since it could be an important predictor of low BMD in the Jordanian population.

Risk Factors for Low Bone Mass in Patients With Ulcerative Colitis Following Ileal Pouch-Anal Anastomosis

OBJECTIVES: Bone mineral density (BMD) can be adversely affected by the chronic nature of inflammatory bowel disease. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) who require proctocolectomy. There are few data on BMD in UC patients with IPAA. The aim of the study was to assess the prevalence and risk factors associated with low BMD in UC patients after IPAA. METHODS: A total of 327 eligible patients with UC and IPAA from the Pouchitis Clinic were enrolled. Dual-energy X-ray absorptiometry was performed. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. A total of 39 demographic and clinical variables were evaluated with logistic regression models. RESULTS: Of 327 patients with a median of 4 years after IPAA, 105 (32.1%) had low BMD. Fragility fracture was documented in 11 patients (10.5%) in the low BMD group and in 13 of 222 patients (5.9%) in the normal BMD group (P=0.14). In the multivariable analysis, covariateadjusted factors associated with a low BMD were advanced age (odds ratio (OR) = 1.64 per 5 years; 95% CI, 1.44-1.87), low body mass index (OR=0.43 per 5 kg/m2; 95% CI, 0.30-0.62), and non-use of daily calcium supplement (OR=0.53; 95% CI, 0.29-0.96). Pouch-associated factors were not found to be significantly associated with the bone loss. CONCLUSIONS: Low BMD was common in patients with UC, even after colectomy and IPAA. Low BMD in this patient population was associated with certain risk factors, some of which may be modifiable.

Risk Factors for Low Bone Mass in Patients With Ulcerative Colitis Following Ileal Pouch-Anal Anastomosis

Bone mineral density (BMD) can be adversely affected by the chronic nature of inflammatory bowel disease. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) who require proctocolectomy. There are few data on BMD in UC patients with IPAA. The aim of the study was to assess the prevalence and risk factors associated with low BMD in UC patients after IPAA. A total of 327 eligible patients with UC and IPAA from the Pouchitis Clinic were enrolled. Dual-energy X-ray absorptiometry was performed. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. A total of 39 demographic and clinical variables were evaluated with logistic regression models. Of 327 patients with a median of 4 years after IPAA, 105 (32.1%) had low BMD. Fragility fracture was documented in 11 patients (10.5%) in the low BMD group and in 13 of 222 patients (5.9%) in the normal BMD group (P=0.14). In the multivariable analysis, covariate-adjusted factors associated with a low BMD were advanced age (odds ratio (OR) =1.64 per 5 years; 95% CI, 1.44-1.87), low body mass index (OR=0.43 per 5 kg/m(2); 95% CI, 0.30-0.62), and non-use of daily calcium supplement (OR=0.53; 95% CI, 0.29-0.96). Pouch-associated factors were not found to be significantly associated with the bone loss. Low BMD was common in patients with UC, even after colectomy and IPAA. Low BMD in this patient population was associated with certain risk factors, some of which may be modifiable.

Prevalence and etiology of low bone mineral density in juvenile systemic lupus erythematosus

Studies of adults with systemic lupus erythematosus (SLE) have frequently demonstrated the presence of decreased bone mineral density (BMD). However, there have been few investigations in pediatric patients to date. This study was undertaken to determine the prevalence of low BMD in patients with juvenile SLE and to identify associated risk factors. We studied 64 consecutive patients with juvenile SLE in whom routine dual x-ray absorptiometry (DXA) scanning was performed. Lumbar spine osteopenia was defined as a BMD Z score of < -1 and > or = -2.5, and osteoporosis as a BMD Z score of < -2.5. Decreased hip BMD was defined as a value of < 80%. Data on disease activity, quality of life, disease-related damage, sex, ethnicity, body mass index, age at diagnosis, age at DXA, medication use and duration, clinical features, and puberty status were collected at the time of DXA. Lumbar spine osteopenia was seen in 24 patients (37.5%) and osteoporosis in 13 (20.3%). Decreased hip BMD was present in 12 patients (18.8%). By univariate analysis, osteopenia was significantly correlated with age, disease duration, duration of corticosteroid use, cumulative corticosteroid dose, azathioprine use, cyclophosphamide use, lupus nephritis, and damage. Two additional variables, mycophenolate mofetil use and class III-IV nephritis, were associated with osteoporosis. Abnormal hip BMD was associated with disease duration, duration of corticosteroid use, and cumulative corticosteroid dose. By multivariate analysis, only disease duration remained in the model for osteoporosis and abnormal hip BMD, while cumulative corticosteroid dose was the variable associated with osteopenia. These results indicate that osteopenia and osteoporosis are common in juvenile SLE and are associated more closely with increased disease duration than with cumulative corticosteroid dose.

Low bone-mineral density in patients with HIV: pathogenesis and clinical significance.

PURPOSE OF REVIEW: Low bone-mineral density is a recently recognized metabolic complication of HIV infection and its treatment. While the clinical impact of low bone-mineral density remains uncertain, the prolongation of survival attributable to more effective antiretroviral therapy has contributed to an aging population of HIV-infected patients who may be prone to developing fragility fractures. RECENT FINDINGS: While most of the available data are on young men, recent publications have increased our understanding of the epidemiology of low bone-mineral density and bone loss in HIV-positive women. Most studies suggest that initiation of certain combinations of antiretroviral agents may be associated with moderate bone loss initially, but bone-mineral density usually stabilizes or improves with longer follow-up. Most studies suggest that, despite lower bone-mineral density, fragility fractures are relatively uncommon in HIV-positive patients, perhaps because of their relative youth. SUMMARY: The pathogenesis of low bone-mineral density in HIV-positive patients is complex and multifactorial, and its clinical impact remains unclear. Further research is needed to clarify the approach to optimal screening and treatment of osteoporosis in the setting of HIV infection.

Risk factors for low bone mineral density (BMD) in pediatric sarcoma survivors

9059 Background: The incidence of and risk factors for low BMD in patients treated for sarcoma in childhood is unknown. Methods: Retrospective medical record review of 99 patients with pediatric sarcoma diagnosed between 12/82 and 2/03 who had undergone QCT evaluation more than 1 year after completion of treatment. Low BMD was defined as &gt;1.5 standard deviations below the mean. A Z-test was used to assess whether BMD was lower in our patient population than in the normal reference population. Logistic regression was used to examine factors predictive of low BMD. Risk factors analyzed included demographic variables, tumor features, treatment exposures, endocrine/renal dysfunction, and health habits. Results: Twenty-six of the 99 sarcoma survivors (26%) had low BMD. The mean (−0.8) and median (−0.75) QCT Z-scores were significantly lower than those of the normal reference population (mean and median = 0, p&lt;0.0001). Factors associated with lower BMD included young age at sarcoma diagnosis (p=0.044) or at QCT measurement (p=0.001), greater weight at diagnosis (p=0.045), non-lower extremity tumor site (p=0.023), higher cumulative cyclophosphamide dose (p=0.007), smaller size at QCT measurement [height (p=0.018), weight (p=0.012)], and low serum creatinine [at diagnosis (p=0.033), at QCT measurement (p=0.014)]. Gender, race, ifosfamide/methotrexate/etoposide exposure, radiotherapy, endocrinopathy, and health habits were not predictive of low BMD. Conclusions: Survivors of childhood sarcoma are at high risk for low BMD. Risk factors include young age, non-lower extremity tumor site, and high cumulative cyclophosphamide exposure. Prospective studies are needed to confirm these risk factors, and to guide implementation of effective screening guidelines and therapeutic measures. No significant financial relationships to disclose.

The Effect of Anti‐TNF‐α Therapy on Spinal Bone Mineral Density in Patients with Crohn's Disease

Proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) might be, at least partially, responsible for the development of osteopenia or osteoporosis in Crohn's disease. We investigated whether anti-TNF therapy for Crohn's disease could have any skeletal impact. Therefore, we studied the effects of infliximab, a monoclonal antibody against TNF-alpha with and without bisphosphonates, on spinal bone mineral density (BMD). The effect of corticosteroids was also analyzed. A retrospective cohort analysis was performed on 61 patients with Crohn's disease and low BMD by serial DXA scans. Twenty-three patients were on infliximab and 36 patients were on bisphosphonates. Mean duration between DXA scans was 2.2 +/- 0.99 years. After controlling for corticosteroid use, patients with concurrent infliximab and bisphosphonate treatment exhibited a greater increase in BMD compared to those on bisphosphonates alone (+6.7%/year vs. +4.46%/year, P= 0.045); corticosteroids inhibited this effect (P= 0.025). However, infliximab alone had no effects on BMD. Patients receiving bisphosphonates showed a significant increase in lumbar spine BMD compared to those not on bisphosphonates (+3.97% change in T score/year vs. -3.68%/year, P < 0.0001). Concurrent corticosteroid use significantly inhibited this effect (+2.15%/year vs. +4.97%/year, P= 0.0014). Concurrent infliximab use may confer an additional benefit to that already documented for bisphosphonate use alone; bisphosphonates are beneficial in the treatment of low BMD in patients with Crohn's disease, though corticosteroids may partially inhibit this effect.

Association of the vitamin D receptor genotype BB with low bone density in hyperthyroidism.

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p < 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p < 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p < 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.

Vitamin D–receptor genotypes as independent genetic predictors of decreased bone mineral density in primary biliary cirrhosis

Background & Aims: Hepatic osteodystrophy is a complication of primary biliary cirrhosis (PBC). Allelic polymorphisms of the vitamin D receptor (VDR) gene are related to bone mineral density (BMD) in normal cohorts and those with primary osteoporosis. We sought to establish the prevalence of reduced bone mass in PBC, correlate BMD with VDR gene polymorphisms, and identify risk factors for the development of hepatic osteodystrophy. Methods: Seventy-two female patients with PBC were evaluated prospectively. Clinical information, BMD assessment, disease severity, and osteoporosis risk factors were documented, and multivariate regression modeling was performed. Results: Twenty-four percent of the patients were osteoporotic at the lumbar spine and 32% at the femur. Severe bone loss (z score <−2.0) occurs 4 times more frequently in patients with PBC compared with controls. Body weight ( P = 0.003) and postmenopausal status ( P = 0.012) correlated independently with BMD. VDR genotype ( P = 0.01) correlated with lower BMD at the spine only. Conclusions: Osteoporosis is a common complication of PBC. VDR genotype predicts lower BMD in patients with PBC. Studies are warranted to investigate the mechanism(s) by which VDR as well as other candidate genes may contribute to the development of hepatic osteodystrophy in PBC. GASTROENTEROLOGY 2000;118:145-151

Three Years' Follow-up of Bone Density in Adult Coeliac Disease: Significance of Secondary Hyperparathyroidism

Background: The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. Methods: One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. Results: SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. Conclusions: Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease.