Erik Trovão Diniz

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.

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.

Bisfosfonatos podem minimizar a fome óssea após paratireoidectomia em pacientes com hiperparatireoidismo primário e osteíte fibrosa cística

OBJECTIVE To assess the effect of bisphosphonates on post-parathyroidectomy hypocalcemia in patients with osteitis fibrosa cystica. METHODS Review of the medical records of six patients using bisphosphonates preoperatively. RESULTS Mean age was 35.6 ± 10.5 years; serum calcium = 13.51 + 0.87 mg/dL; iPTH = 1,389 + 609 pg/mL. The mean value of urine deoxypyridinoline (UDPD) of three patients was 131 ± 183 nmol/mmol Cr, and of C-telopeptide (CTX), 2,253 ± 1,587 pg/mL. The mean values of bone densitometry (T score) were as follows: 0.673 ± 0.150 g/cm(2) (-4.42 ± 1.23) in lumbar spine (L2-L4); 0.456 ± 0.149 g/cm(2) (-5.58 ± 1.79) in the femoral neck; and 0.316 ± 0.055 g/cm(2) (-5.85 ± 0.53) in radius 33. Patient 1 received oral alendronate, 30 mg/day for four weeks; his calcium decreased from 14 to 11.6 mg/dL, and his UDPD from 342 to 160 nmol/mmol Cr. Patient 2 received oral alendronate, 20 mg/day for six weeks; his calcium decreased from 14 to 11.0 mg/dL and his UDPD from 28.8 to 14 nmol/mmol Cr. Patient 3 received intravenous pamidronate, 90 mg prior to surgery. Patient 4 received oral alendronate, 140 mg/week for six weeks; her calcium decreased from 13.7 to 12.3 mg/dL and her CTX from 2,160 to 1,340 pg/mL. Patient 5 received oral alendronate, 140 mg/ week for six weeks; her calcium levels dropped from 14.3 to 14.1 mg/dL; her CTX did not change. Patient 6 received ibandronate, 150 mg, ten days prior to surgery; his CTX reduced by 62%. No patient developed severe hypocalcemia in the first postoperative week. One year after surgery, the mean gain in bone mineral density was 40% ± 29% in L2-L4, 86 ± 39% in the femoral neck, and 22% ± 11% in radius 33. CONCLUSION The preoperative use of bisphosphonates seems to attenuate bone hunger without preventing a significant increase in bone mass in the follow-up of parathyroidectomy.

Factors associated with secondary hyperparathyroidism in premenopausal women undergoing Roux-en-Y gastric bypass for the treatment of obesity

OBJECTIVE To evaluate bone metabolism, bone density (BMD) and vertebral fractures in morbidly obese individuals. SUBJECTS AND METHODS Case series of 29 premenopausal obese patients, 15 of whom had been submitted to bariatric surgery. Serum calcium, albumin, PTH and 25-hydroxy vitamin D (25OHD) were measured as well as bone densitometry of the lumbar spine and proximal femur, and lateral spine x-rays. RESULTS High parathyroid hormone (PTH) levels were recorded in 46.6% of the surgical patients and in 21.4% of the non-surgical patients (p = 0.245); 26.7% of the former and 28.6% of the latter revealed levels 25OHD < 30 ng/mL (p = 1.000). Calcium intake was higher in the surgical group (p = 0.004) along with lower serum calcium concentrations (p = 0.019). There were no significant differences in bone mineral density (BMD) or in the prevalence of vertebral fractures between groups. CONCLUSION In premenopausal women undergoing Roux-en-Y gastric bypass there is important intestinal calcium mal absorption which seems to be the main factor causing secondary hyperparathyroidism.

Novel nonsense mutation (p.Y113X) in the human growth hormone receptor gene in a Brazilian patient with Laron syndrome

BACKGROUND To date, about sixty different mutations within GH receptor (GHR) gene have been described in patients with GH insensitivity syndrome (GHI). In this report, we described a novel nonsense mutation of GHR. METHODS The patient was evaluated at the age of 6 yr, for short stature associated to clinical phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products from exons 2-10 were sequenced. RESULTS The patient had high GH (26 microg/L), low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5 disclosed adenine duplication at nucleotide 338 of GHR coding sequence (c.338dupA) in homozygous state. CONCLUSION We described a novel mutation that causes a truncated GHR and a loss of receptor function due to the lack of amino acids comprising the transmembrane and intracellular regions of GHR protein, leading to GHI.

Prevalence of cortical osteoporosis in mild and severe primary hyperparathyroidism and its relationship with bone markers and vitamin D status.

Studies on the prevalence of site-specific osteoporosis in patients with different clinical presentations of primary hyperparathyroidism (PHPT) are scarce in the literature. The present study aims to determine the prevalence of cortical osteoporosis in such patients by using 3-site dual-energy X-ray absorptiometry (lumbar spine, femoral neck, 1/3 radius). We studied 49 patients, 12 males and 37 females, with PHPT, who were separated into 3 groups: asymptomatic (AS), renal stone disease (RS), and osteitis fibrosa cystica (OF). Osteoporosis occurred as follows: lumbar spine-48% for AS, 17.6% for RS, and 100% for OF (p=0.0004); femoral neck-20% for AS, 12% for RS, and 85.7% for OF (p=0.0014); 1/3 radius-71% for AS, 53% for RS, and 86% for OF (p=0.2845). Serum calcium, parathyroid hormone, alkaline phosphatase, and beta-carboxy-terminal telopeptide were significantly higher in the OF group. The mean values for 25-hydroxyvitamin D were lower in OF group than AS and RS groups (15.2+/-6.3 ng/mL vs. 22.7+/-11.9 ng/mL and 20.3+/-7.0 ng/mL; p=0.2139). Based on these results, we conclude that the prevalence of osteoporosis is high in all sites studied and is almost universal in the OF patients. The great prevalence of cortical osteoporosis is seen even in young patients with less severe forms of the disease.

Short-term bone marker responses to teriparatide and strontium ranelate in patients with osteoporosis previously treated with bisphosphonates

OBJECTIVE To evaluate the responses of serum beta-CTX and osteocalcin in patients who were undergoing treatment with teriparatide or strontium ranelate (SR). SUBJECTS AND METHODS We analyzed 14 patients (12 women and 2 men; mean age of 71 years) taking teriparatide, and 13 female patients (mean age of 70 years) taking SR; all the patients having previously been on bisphosphonates. Serum beta-CTX and osteocalcin levels were determined before and after the first and third months of teriparatide treatment and up to the fourth month of treatment with SR. RESULTS We observed an initial significant increase in osteocalcin levels during the first month (165%, p = 0.01) followed by a peak of beta-CTX (180%, p = 0.02) after the third month of treatment with teriparatide. An increase in these markers was also observed with SR: 49% in osteocalcin (p = 0.002) and 80% in beta-CTX (p = 0.008). CONCLUSION SR had a predominantly short-term bone-forming effect in postmenopausal women with osteoporosis previously treated with bisphosphonates in a lesser degree than with teriparatide.

Primary hyperparathyroidism is associated with subclinical peripheral neural alterations.

OBJECTIVE Some case reports have suggested primary hyperparathyroidism (PHPT) and peripheral polyneuropathy (PPN) are associated; however, there are no reports of studies examining this possible relationship. The aim of this study was to evaluate peripheral nerve conduction in subjects with PHPT. METHODS The study involved 17 patients with PHPT. Mean patient age was 60.5 ± 12.9 years, serum calcium concentration was 11.5 ± 1.0 mg/dL, and the serum parathyroid hormone (PTH) level was 315 ± 569 pg/dL. The control group comprised 17 individuals without PHPT. The mean age of controls was 60.8 ± 12.5 years and the serum calcium concentration was 9.8 ± 0.3 mg/dL. Motor and sensory nerve conduction was assessed by electroneurography (ENG). RESULTS The following ENG parameters differed significantly between the PHPT and control groups: right (R) sural sensory nerve action potential conduction velocity (52.7 ± 6.3 m/s versus 58.0 ± 8.0 m/s; P = .041); R median compound muscle action potential (CMAP) amplitude (7.4 ± 1.6 mV versus 8.9 ± 1.7 mV; P = .002); R median CMAP latency (4.3 ± 1.2 ms versus 3.6 ± 0.6 ms; P = .032); R tibial CMAP latency (4.2 ± 1.1 ms versus 3.3 ± 0.4 ms; P = .001). The neurological examination was normal in all patients. CONCLUSION Our data demonstrate an association between PHPT and peripheral neurological alterations, consistent with subclinical sensory-motor PPN.

Bioavailability of vitamin D3 in non-oily capsules: the role of formulated compounds and implications for intermittent replacement

OBJECTIVE To evaluate the bioavailability of vitamin D in capsules as compared with oily drops in nuns living in a closed community with very low sun exposure. METHODS A randomized, 2 x 2 crossover, open clinical trial was conducted, with 18 nuns aged between 20 and 75 years. Samples were collected in the fasting state and at 4, 8, 12 and 24 hours following the administration of capsules and oily drops (both containing vitamin D3 66,000 UI plus vitamin A 13,200 UI) to determine serum 25 hydroxyvitamin D concentrations (25OHD), at baseline and 90 days after. The evaluation was based on the maximum concentration (Cmax) and area under the curve (AUC0-24). RESULTS The capsule formulation presented Cmax and AUC0-24, 5.78% and 0.76%, respectively, greater than the oily drops formulation. CONCLUSION Both formulations were within the limits for a bioequivalence study, namely C-90% for Cmax and AUC0-24, and the drugs were considered bioequivalent.

Prevalence of vitamin D deficiency is higher in patients with Paget's disease of bone compared with age-matched controls

OBJECTIVE To investigate if vitamin D deficiency is more prevalent in patients with Pagets disease of bone (PDB) than in age-matched controls. SUBJECTS AND METHODS We measured serum 25-OHD in 28 untreated patients with PDB and two control groups: 284 elderly men from an ongoing cohort from our department, and 151 postmenopausal women seen in our outpatient clinic for routine medical evaluation. RESULTS The mean ± SD serum 25-OHD was significantly lower in subjects with PDB (23.76 ± 6.29 ng/mL) than in the control groups of elderly men (27.86 ± 13.52 ng/mL) and postmenopausal women (30.30 ± 9.59 ng/mL), p = 0.015. The prevalence of vitamin D deficiency considering a cut-off point of serum 25-OHD < 30 ng/mL was 85.7% in patients with PDB, and in elderly men and postmenopausal women it was 66.7 % and 54.3%, respectively (p < 0.001). CONCLUSION These results suggest a high prevalence of hypovitaminosis D in patients with Pagets disease living in the tropics.