Luiz Griz

Vitamin D deficiency: a global perspective

Vitamin D is essential for the maintenance of good health. Its sources can be skin production and diet intake. Most humans depend on sunlight exposure (UVB 290-315 nm) to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by the skin, leading to transformation of 7-dehydrocholesterol into vitamin D3 (cholecalciferol). Season, latitude, time of day, skin pigmentation, aging, sunscreen use, all influence the cutaneous production of vitamin D3. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risk for other morbidities such as cardiovascular disease, type 1 and type 2 diabetes mellitus and cancer, especially of the colon and prostate. The prevalence of hypovitaminosis D is considerable even in low latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis. Although severe vitamin D deficiency leading to rickets or osteomalacia is rare in Brazil, there is accumulating evidence of the frequent occurrence of subclinical vitamin D deficiency, especially in elderly people.

Prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus and their relationship with duration of the disease and chronic complications

UNLABELLED Controversial data suggest that patients with type 2 diabetes mellitus have an increased risk of fractures despite having, in some studies, higher bone mineral density. METHODS The aim of this study was to determine the prevalence of osteoporosis and morphometric vertebral fractures in 148 postmenopausal diabetic women, aged 61.87±7.85 years, and their relationship with clinical and metabolic factors and chronic complications of the disease. RESULTS The prevalence of osteoporosis was 30.4% at lumbar spine (LS) and 9.5% at femoral neck (FN). The prevalence of vertebral fractures was 23%, mostly mild and located at the thoracic spine. Patients with fractures were older (P<.001), had been in the menopause for a long period (P=.005), had lower creatinine clearance (P=.026) had and lower bone mineral density at LS (P=.01) and FN (P=.042). The frequency of fractures increased with age (P<.001), with the duration of the disease (P=.037) and with the presence of retinopathy (P=.030). In patients with fractures, the prevalence of osteoporosis increased to 40% at LS (P=.004) and to 35.7% at FN (P=.049). After logistic regression adjustment, it was observed that the likelihood of presenting vertebral fractures was significantly increased at the age of 60 years or older (P<.001) and with the presence of osteoporosis at LS (P=.006), irrespective of blood glucose control. CONCLUSION We found a high prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus, irrespective of blood glucose control, and these conditions were more frequent in long-standing disease and in patients with retinopathy and impaired renal function.

Vitamin D deficiency and its relationship with bone mineral density among postmenopausal women living in the tropics

OBJECTIVE To determine vitamin D (25OHD) status and its relationship with bone mineral density (BMD) in 93 postmenopausal women. SUBJECTS AND METHODS Patients were distributed in two groups: Group 1 - 51 to 65 years (n = 45) and Group 2 - 66 to 84 years (n = 48); 25OHD and PTH serum were analyzed and a DXA scan of the lumbar spine (LS) and femoral neck (FN) were taken. RESULTS Mean +/- SD of serum 25OHD levels were 80.6 +/- 43.3 nmol/L (Group 1) and 63.7 +/- 27.6 nmol/L (Group 2); 24% had 25OHD levels < 25 nmol/L and 43.7% < 50 nmol/L. The prevalence of vitamin D deficiency at the 62.5 nmol/L cutoff increased significantly with age. Patients with hypovitaminosis D had a lower BMD at the FN (0.738 +/- 0.102 vs. 0.793 +/- 0.115 g/cm, p = 0.03) and had been postmenopausal for longer (21.0 +/- 8.4 vs. 16.2 +/- 8.4 years, p = 0.01). CONCLUSION We found a high prevalence of hypovitaminosis D in postmenopausal women. Age, years elapsed since menopause and low BMD in the FN were associated with deficiency.

From mild to severe primary hyperparathyroidism: the Brazilian experience

Primary hyperparathyroidism often presents as an asymptomatic disorder. In our institution, routine serum calcium measurements have now been used as part of medical examination for 23 years. Out of 124 patients consecutively seen at our institution, 47% presented with no symptoms related to the disease, while 25% presented with severe skeletal involvement and osteitis fibrosa cystica, 25% with renal stone disease without overt bone involvement, and 2% with the typical neuropsychiatric syndrome. This same pattern is seen in the city of São Paulo. In severe disease pathological fractures are frequently seen, especially in long bones of the lower extremities, and also loss of lamina dura of the teeth and salt-and-pepper appearance of the skull. Bone mineral density is extremely low in these patients but usually show remarkable recovery following surgical cure. Serum PTH and bone markers are considerable higher in severely affected patients, who also have a high rate of vitamin D deficiency, and the parathyroid lesion is easier located compared with asymptomatic patients. From pathological specimens 87% had histological confirmation of a single adenoma, 6.4% multiple gland hyperplasia and 3.8% carcinoma.

Paget's disease of bone

Pagets disease of bone is a focal disorder of bone remodeling accompanied initially by an increase in bone resorption, followed by a disorganized and excessive formation of bone, leading to pain, fractures and deformities. It exhibits a marked geographical variation in its prevalence. In Brazil it predominantly affects persons of European descent. The majority of the reported cases of the disease in Brazil are from Recife, owing to its peculiar mixed European colonization over approximately four centuries. The etiology is complex and involves both genetic and environmental factors. The disease is often asymptomatic and diagnosis is usually based on biochemical markers of bone turnover, radionuclide bone scan and radiological examination. Bisphosphonates, in particular zoledronic acid, are regarded as the treatment of choice for Pagets disease of bone.

Evidence-based non-skeletal actions of vitamin D

Vitamin D is a major regulator of mineral homeostasis through its action in the kidney, intestine, bone and parathyroid glands. On these tissues, its active form, calcitriol, acts by binding to a specific nuclear receptor that belongs to the steroid/thyroid hormone receptor family. This receptor, however, has also been identified in several additional human tissues. So, apart from its traditional actions related to calcium, vitamin D and its synthetic analogs are being increasingly recognized for their anti-proliferative, pro-differentiative and immunomodulatory activities. Low levels of vitamin D have been linked to many chronic diseases. Decreased muscle function and increased fall risk in elderly people; prostate, breast and colorectal cancers; diabetes mellitus; and other health problems have been associated to low circulating levels of 25-hydroxyvitamin D. This paper presents an overview of the available scientific evidence for the non-calcemic actions of vitamin D in humans.

RELATIONSHIP BETWEEN SERUM VITAMIN D STATUS AND CLINICAL MANIFESTATIONS OF PRIMARY HYPERPARATHYROIDISM

OBJECTIVE To compare vitamin D status represented by serum 25-hydroxyvitamin D (25-OHD) levels in a group of patients with primary hyperparathyroidism, stratified by clinical manifestations. METHODS We studied 22 patients (18 women and 4 men) with primary hyperparathyroidism--5 patients with severe osteitis fibrosa cystica, 10 symptomatic patients with active renal stone disease without overt bone disease, and 7 asymptomatic patients. Bone mineral density (BMD) measurements (T-scores) were done at the lumbar spine, femoral neck, and distal radius, and laboratory data for the three subgroups were analyzed. RESULTS Although considerably younger than the asymptomatic group, patients with osteitis fibrosa had significantly lower mean serum 25-OHD levels (16.7 +/- 1.1 ng/mL versus 29.9 +/- 2.9 ng/mL; P = 0.003). Moreover, patients with osteitis fibrosa had significantly lower BMD in comparison with patients who had renal stone disease as well as asymptomatic patients for all sites measured. Serum parathyroid hormone levels were significantly higher in patients with osteitis fibrosa than in asymptomatic patients (1,352.8 +/- 297.2 pg/mL versus 145.0 +/- 43.7 pg/mL; P<0.02) as well as in comparison with patients who had renal stone disease (P<0.02). Patients with osteitis fibrosa had urinary N-telopeptide levels that were significantly higher than those in asymptomatic patients (501.5 +/- 201.7 versus 51.3 +/- 6.4 nmol/mmol creatinine; P = 0.02) and those in patients with renal stone disease (P = 0.01). CONCLUSION The findings in this study demonstrate that vitamin D deficiency or insufficiency may contribute to disease severity in primary hyperparathyroidism.

Prevalence of central obesity in a large sample of adolescents from public schools in Recife, Brazil

OBJECTIVE To determine the prevalence and association of central obesity (CO) and hypertension and its associations with alcohol intake, smoking and physical activity in adolescents. SUBJECTS AND METHODS Cross sectional study in 1,824 students from 29 public schools in Recife. RESULTS 89.6% were normal weight, 6.7% overweight and 3.7% obese; 77.2% were normotensive, 5.9% prehypertensive and 16.9% hypertensive; CO was 10.2% when the 90th percentile was used as cutoff and 25.2% when the 75th percentile was used. There was a higher likelihood of central obesity among students aged 18 to 20 years, smoking and alcohol intake. The probability of hypertension increases if the subject is male, has a waist circumference (WC) ≥ 90, WC ≥ 75 and does not practice physical activity. CONCLUSIONS A high prevalence of CO and hypertension was found in adolescents. CO was more frequent in students aged 18 to 20 years, smokers and with alcohol intake and hypertension was associated with male, CO and no physical activity.

Metabolic Syndrome and Central Fat Distribution Are Related to Lower Serum Osteocalcin Concentrations

Background: The aim of this study was to evaluate the association of serum osteocalcin with the metabolic syndrome (MS) in men and premenopausal women. Methods: 14 middle-aged men and 44 premenopausal women were evaluated. MS was defined according to the International Diabetes Federation criteria. Anthropometric data were collected and serum osteocalcin, serum C-telopeptide (CTX), fasting plasma glucose (FPG) and lipid profile measured. Results: The mean age was 41.07 ± 8.4 years and did not differ between patients with and without MS. Mean osteocalcin was significantly lower in patients with MS (11.18 ± 4.62 vs. 15.09 ± 5.05, p = 0.003) and decreased significantly with the rise in the number of criteria for diagnosis of MS. There were no significant differences in serum CTX between the two groups. Serum osteocalcin was lower in patients with body mass index (BMI) ≥25 (p = 0.038) and FPG ≥100 mg/dl (p = 0.024), and in hypertensive (p = 0.013) and diabetic patients (p = 0.036), and was inversely associated with BMI (p = 0.024), waist circumference (WC) (p = 0.024), FPG (p = 0.007) and systolic blood pressure (SBP) (p = 0.037). Conclusion: This study showed that lower serum osteocalcin is associated with the presence of MS and that osteocalcin is inversely associated with BMI, WC, FPG and SBP, suggesting that osteocalcin plays a part in the development of MS.

Differences in Accuracy of 99mTc-Sestamibi Scanning Between Severe and Mild Forms of Primary Hyperparathyroidism

Preoperative localization of the parathyroids using 99mTc-sestamibi scanning has not yet been established as a routine diagnostic procedure for primary hyperparathyroidism. Several studies have demonstrated a variable degree of accuracy (70%–98%) in asymptomatic patients. Methods: We evaluated the accuracy of this technique in 64 patients who underwent scanning between January 2000 and January 2005 according to the clinical manifestations of the disease. Results: The study included 25 asymptomatic patients (group I), 18 nephrolithiasis patients without overt bone disease (group II), and 21 patients with severe bone involvement and osteitis fibrosa cystica (group III). Mean serum calcium in groups I, II, and III was 10.98 ± 0.02, 11.32 ± 0.17, and 13.35 ± 0.35 mg/dL, respectively. Mean serum parathyroid hormone in groups I, II, and III was 135.45 ± 13.50, 165.85 ± 15.06, and 579.6 ± 628.4 pg/mL, respectively. The 99mTc-sestamibi scan results were positive in 64% of the patients in group I, in 83% of those in group II, and in 100% of those in group III. Of the patients with severe bone disease, 70% showed increased uptake on the initial images, whereas in the other groups, increased uptake was seen only on the delayed images, as expected. Conclusion: Our data show a high degree of accuracy for the use of 99mTc-sestamibi scanning as a localizing procedure in severe primary hyperparathyroidism.