Risk Factors for Low Bone Density in Inflammatory Bowel Disease: Use of Glucocorticoids, Low Body Mass Index, and Smoking.

BACKGROUND: Inflammatory bowel disease (IBD) patients are reported to have lower bone density compared to healthy controls. There is limited consensus regarding factors affecting bone density among these patients. Our aim, therefore, was to determine clinical and genetic variables that contribute to lower bone mineral density (BMD) in IBD patients. METHODS: A cross-sectional study of IBD patients treated in a tertiary referral center was performed. Epidemiological and clinical data were collected, and genetic testing for the common mutations in Nucleotide-binding Oligomerization Domain-containing protein (NOD)2 was performed. We examined correlations between the different variables and BMD in the total hip, femoral neck, and lumbar spine. RESULTS: Eighty-nine patients (49% males, 67 Crohn's disease [CD]) participated in the study. 42Forty-two (63%) of the CD and 13 (59%) of the ulcerative colitis patients met the criteria for osteoporosis/osteopenia. Factors associated with lower Z scores were low body mass index (BMI; r = -0.307, p = 0.005), use of glucocorticoids (likelihood ratio [LR] 5.1, p = 0.028), and a trend for male gender (LR = 3.4, p = 0.079). Among CD patients, low bone density showed borderline significance for association with gastrointestinal surgery (LR = 4.1, p = 0.07) and smoking (LR = 3.58, p = 0.06). Low levels of 25OHD were not associated with low BMD, nor were mutations in NOD2. No increased rate of fractures was seen among patients with osteopenia or osteoporosis. CONCLUSION: In addition to the generally accepted risk factors for osteoporosis (glucocorticoids, low BMI, smoking), male IBD patients had a trend toward lower BMD. Carrying a mutaticon in NOD2 did not confer a risk for bone loss.

[SHOULD PATIENTS WITH PRIMARY HYPERPARATHYROIDISM AND NEGATIVE IMAGING STUDIES BE REFERRED TO SURGERY?]

INTRODUCTION: Parathyroidectomy is the only curative treatment for primary hyperparathyroidism (PHPT). In cases where imaging fails to demonstrate an adenoma, a bilateral neck exploration (BNE) is performed. Negative imaging is thought to predict surgical failure, and patients with negative imaging are often not referred for surgery. These patients are at risk for disease progression. AIMS: Evaluate the effect of negative imaging on surgical findings and the cure rate in patients with PHPT. METHODS: A total of 133 patients underwent parathyroidectomy for PHPT. Data were retrospectively retrieved including preoperative imaging, surgical findings and results. A comparison was conducted between patients with negative and positive imaging. The main outcome measure was cure. RESULTS: A negative MIBI (methoxy-isobutyl-isonitrile) scan was seen in 30 (22%) patients and a negative US in 46 (34.5%). Patients with negative MIBI scan more commonly underwent BNE compared with patients with a positive scan (53% vs. 25%, respectively, p=0.0046). Patients with negative imaging had a significantly higher rate of multigland disease compared with patients with positive imaging (35% vs. 12%, p=0.004, for the MIBI scan; 27% vs. 12%, p=0.024, for the US, respectively). Overall cure rate was 96%. Highest cure rates were seen in patients with both positive MIBI and US (99% cure rate) and lowest cure rates of 67% in patients with triple negative imaging (MIBI scan, US and 4DCT (Dual computed tomography)) (p=0.003). CONCLUSIONS: Localization of an adenoma in preoperative imaging predicts very high cure rates in patients with PHPT. Negative imaging increases the risk for multigland disease and is associated with lower cure rates.

Vitamin D deficiency in oncology patients--an ignored condition: impact on hypocalcemia and quality of life.

BACKGROUND: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates. OBJECTIVES: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients. METHODS: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 +/- 13 years treated with intravenous bisphosphonates. RESULTS: Most of the patients (n = 44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 +/- 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH) D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 - 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 +/- 191 ng/ml) but not with CTX levels (mean 0.265 +/- 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99). CONCLUSIONS: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.

Hip fractures in the elderly in Israel-possible impact of preventable conditions.

In the present study we evaluated the possible contribution of different factors to the occurrence of hip fractures in Israel. We assessed medical history, physical activity, body mass index, smoking status, bone turnover markers and calcium regulating hormones levels of 142 consecutive elderly hip fracture patients (HFP), and compared them to 96 community dwelling elderly people without a history of hip fracture. Age and female gender were the strongest predictors of hip fracture, p<0.001 and 0.013. Stepwise logistic regression demonstrated that HFP had higher PTH and lower 25(OH)D(3) levels, p=0.002, p<0.001; they were less physically active, p<0.001, and had higher rate of vitamin D insufficiency during winter-spring, compared to summer-autumn, p=0.033. Diabetics had higher risk for hip fracture, p=0.06, OR=3.9 (95% CI 1.50-10.4). Deoxypyridinoline (DPD) cross links levels were 19.35+/-10.58mg/mg creatinine in HFP and 9.12+/-3.52 in controls, p<0.0001. Bone alkaline phosphatase (BAP)/DPD ratio was 1.5 in controls compared to 0.53 in HFP. We conclude that age and female gender were the strongest predictors for hip fracture. Diabetic patients had threefold risk for hip fracture. Bone formation/bone resorption ratio was lower in HFP. Vitamin D deficiency and physical inactivity are important preventable risk factors for hip fracture.

Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients.

BACKGROUND: Different dosing protocols have been used for vitamin D supplementation, but there has been a lack of comparative data among them. OBJECTIVE: Our objective was to determine whether the same cumulative dose of vitamin D3 produces different effects if it is given daily, weekly, or monthly. DESIGN: Women, age 81 +/- 8 yr (+/- sd, n = 48), who had undergone surgery to repair hip fracture were randomized to vitamin D3-supplementation protocols at 1,500 IU daily, or 10,500 IU once weekly, or 45,000 IU once every 28 d. The primary outcome measure was the serum 25-hydroxyvitamin D [25(OH)D] concentration attained. RESULTS: Initially, serum 25(OH)D concentrations for daily, weekly, and monthly groups were, respectively, 15.13 +/- 6.9, 15.7 +/- 10.1, and 16.2 +/- 10.1 ng/ml. By d 7, these had increased significantly in all the groups (P < 0.001). On the first day after the monthly dose, both serum 25(OH)D and serum 1,25-dihydroxyvitamin D had increased significantly (P < 0.012 each), whereas these did not change significantly on the day after daily or weekly doses. After 2 months, serum 25(OH)D with daily, weekly, and monthly dosing were, respectively, 33.2 +/- 8.5, 29.2 +/- 8.9, and 37.1 +/- 10.3 ng/ml; there were no significant differences among these values. CONCLUSIONS: Supplementation with vitamin D can be achieved equally well with daily, weekly, or monthly dosing frequencies. Therefore, the choice of dose frequency can be based on whichever approach will optimize an individual's adherence with long-term vitamin D supplementation.

Sialochemical and oxidative analyses in radioactive I131-treated patients with thyroid carcinoma.

BACKGROUND: I131 in relatively high doses has been shown in the past to cause damaging salivary effects and oral discomfort in patients. Although lower dosage is now widely accepted, I131 may still be the source of salivary damage over the long-term and subsequent harmful effects on both the oral cavity and the gastrointestinal tract, into which the saliva is swallowed. This study examined the effects of radioactive I131 on salivary gland activity, saliva composition and oxidative profile, and related oral discomfort complaints following thyroidectomy due to carcinoma of thyroid gland. METHODS: Out of 40 consenting female post-thyroidectomy patients, 23 (mean age 50+/-4 years old) were treated with I131 while 17 (mean age 46+/-4) were not. Whole saliva from all subjects was analyzed for antioxidant and biochemical composition and flow rate. RESULTS: The salivary flow rates of both groups were similar but their composition differed considerably. Salivary superoxide dismutase enzyme (SOD), total protein, and albumin concentrations were significantly reduced in the treated patients by 40, 25, and 18% respectively (P<0.05), as were all other salivary antioxidants. Oral discomfort complaints were far more prevalent in the I131-treated patients. CONCLUSIONS: I131-dependent damage to the salivary glands was evidenced by a broad spectrum of compositional alterations and oral complaints. Reduction in salivary antioxidant status, SOD enzyme, and the uric acid molecule leaves the oral cavity less protected against oxidative stress. This is the first report of radioactive I131 treatment being harmful to salivary glands due to compromised salivary compositional and oxidative profile and oral discomfort complaints.

Current criteria for hip fracture risk assessment--are we missing something?

BACKGROUND: Hip fracture rates are increasing worldwide, and the risk for a second hip fracture is high. The decision to administer antiresorptive treatment is based mainly on bone mineral density and/or a history of previous osteoporotic fractures. OBJECTIVES: To evaluate the contribution of BMD, previous fractures, clinical and laboratory parameters to hip fracture risk assessment. METHODS: The study population included 113 consecutive hip fracture patients, aged 72.5 +/- 9.4 years, discharged from the orthopedic surgery department. BMD was assessed at the lumbar spine, femoral neck and total hip. The results were expressed in standard deviation scores as T-scores--compared to young adults and Z-scores--compared to age-matched controls. Plasma or serum levels of parathyroid hormone, 25-hydroxyvitamin 3 and urinary deoxypyridinoline cross-links were evaluated. RESULTS: We observed T-scores < or = 2.5 in 43 patients (45.3%) at the lumbar spine, in 47 (52.2%) at the femoral neck and in 33 (38%) at the total hip. Twenty-eight patients (29.5%) had neither low BMD nor previous osteoporotic fractures. Using a T-score cutoff point of (-1.5) at any measurement site would put 25 (89%) of these patients into the high fracture risk group. Mean DPD level was 15.9 +/- 5.8 ng/mg (normal 4-7.3 ng/mg creatinine). Vitamin D inadequacy was observed in 99% of patients. CONCLUSIONS: Using current criteria, about one-third of elderly hip fracture patients might not have been diagnosed as being at risk. Lowering the BMD cutoff point for patients with additional risk factors may improve risk prediction yield.

Minimally invasive surgery for treatment of hyperparathyroidism.

BACKGROUND: Minimal invasive surgery for parathyroidectomy has been introduced in the treatment of hyperparathyroidism. OBJECTIVE: To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy. METHODS: Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH measurements for intraoperative assessment. RESULTS: Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5, and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma. CONCLUSIONS: Preoperative localizationof the parathyroid gland by MIBI and ultrasound together with intraoperative iPTH measurements resulted in an overall cure rate of 98.6% for the entire series, The addition of ultrasound to the MIBI scan increased the accuracy of adenoma detection.

Compliance of osteoporotic patients with different treatment regimens.

BACKGROUND: The treatment of osteoporosis among postmenopausal women represents a major public health challenge since long-term therapy is needed to prevent fractures and chronic disability. OBJECTIVES: To assess compliance with osteoporosis drug therapy among Israeli postmenopausal women treated with either a bisphosphonate (alendronate) or a selective estrogen receptor modulator (raloxifene); to identify factors affecting compliance among these patients; and to compare adherence to the treatment in these two groups. METHODS: Our study included 178 consecutive patients aged 67.41 +/- 8.52 years who were treated for osteoporosis with alendronate or raloxifene in the Metabolic Bone Diseases Unit. All the patients received supplementation with calcium carbonate 1,500 mg and 600 IU vitamin D daily. Compliance was assessed at a clinic visit 6 months after starting therapy. RESULTS: The dropout rate was 23% (41 patients): 20 patients (31%) in the raloxifene group and 21 (18%) in the alendronate group (P = 0.0041). The main reasons for dropout were side effects and/or noncompliance, 16 and 24 patients (39% and 58.53%) respectively. The most frequent side effect was abdominal pain in 9 patients (42.8%) who discontinued alendronate use. The reasons for non-compliance were a fear of side effects and high drug price in 6 (30%) and 4 (20%) patients respectively in the raloxifene group, and inconvenience caused by medication use in 3 patients (14.3%) in the alendronate group. Logistic regression analysis of factors that may influence compliance included age, previous fractures, family history of osteoporosis, bone density T-score less than -2.5, and presence and number of concomitant diseases. Age was the only statistically significant parameter in this model: 67.8 +/- 8.8 in non-compliant versus 64.11 +/- 7.4 in compliant patients (P = 0.029). CONCLUSION: At least 20% of the patients discontinued chronic treatment for osteoporosis during the initial 6 months of therapy. The main reasons were gastrointestinal side effects in the alendronate group and fear of side effects and high drug price in the raloxifene group. Older age was the only statistically significant factor influencing compliance.