Marise Lazaretti-Castro

Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial

Aims: To investigate the effects of a 6-month supplementation with calcium and cholecalciferol on biochemical parameters and muscle strength of institutionalized elderly. Methods: This prospective, double-blind, placebo-controlled, randomized trial included Brazilian institutionalized people ≥60 years of age receiving a 6-month supplementation (December to May) of daily calcium plus monthly placebo (calcium/placebo group) or daily calcium plus oral cholecalciferol (150,000 IU once a month during the first 2 months, followed by 90,000 IU once a month for the last 4 months; calcium/vitamin D group). Fasting blood samples for 25(OH)D, PTH and calcium determination were collected (n = 56) and muscle tests were performed (n = 46) to measure the strength of hip flexors (SHF) and knee extensors (SKE) before (baseline) and after the 6-month intervention (6 months). Results: Due to seasonal variations, serum 25(OH)D significantly enhanced in both groups after treatment, but the calcium/vitamin D group had significantly higher 25 (OH)D levels than the calcium/placebo group (84 vs. 33%, respectively; p < 0.0001). No cases of hypercalcemia were observed. While the calcium/placebo group showed no improvement in SHF and SKE at 6 months (p = 0.93 and p = 0.61, respectively), SHF was increased in the calcium/vitamin D group by 16.4% (p = 0.0001) and SKE by 24.6% (p = 0.0007). Conclusions: The suggested cholecalciferol supplementation was safe and efficient in enhancing 25(OH)D levels and lower limb muscle strength in the elderly, in the absence of any regular physical exercise practice.

Hypoparathyroidism and pseudohypoparathyroidism

The principal function of the parathyroid hormone (PTH) is maintenance of calcium plasmatic levels, withdrawing the calcium from bone tissue, reabsorbing it from the glomerular filtrate, and indirectly increasing its intestinal absorption by stimulating active vitamin D (calcitriol) production. Additionally, the PTH prompts an increase in urinary excretion of phosphorus and bicarbonate, seeking a larger quantity of free calcium available in circulation. Two mechanisms may alter its function, limiting its control on calcium: insufficient PTH production by the parathyroids (hypoparathyroidism), or a resistance against its action in target tissues (pseudohypoparathyroidism). In both cases, there are significantly reduced levels of plasmatic calcium associated with hyperphosphatemia. Clinical cases are characterized by nervous hyperexcitability, with paresthesia, cramps, tetany, hyperreflexia, convulsions, and tetanic crisis. Abnormalities such as cataracts and basal ganglia calcification are also typical of these diseases. Treatment consists of oral calcium supplementation associated with increased doses of vitamin D derivatives.

High prevalence of vertebral deformity in premenopausal systemic lupus erythematosus patients

In this paper we searched for vertebral deformities in a group of 70 premenopausal systemic lupus erythematosus (SLE) patients (31.8 ± 8.1 years old) and compared them to a matched control group of 22 healthy women (32.0 ± 8.9 years old). Patients and controls performed spine X-ray (XR) morphometry and lumbar spine and femoral neck bone mineral density (BMD). Clinical data was obtained by a questionnaire and charts review. Thoracic or lumbar spine fracture was observed in 15 (21.4%) SLE patients, while no deformities were found in the control group (P = 0.018). BMD was not different amongst SLE patients and controls and between SLE patients with or without deformities. Although BMD could not predict what patient have deformity, seven patients (46.6%) with deformity had a lumbar spine or femoral neck Z-score less than -1 SD [median = -0.59 (-3.72 to +0.88) and -0.20 (-4.05 to +1.87)] respectively. In addition, we found a negative correlation between number of fracture per patient and lumbar spine and femoral neck BMD (R = 0.58, P = 0.04 and R = 0.84, P = <0.0001 respectively). No significant correlation was found between number of deformities and clinical data. This is the first study to search for vertebral deformities in SLE patients and to demonstrate a high prevalence of deformities in a relative young SLE population. These findings bring up the necessity to look for spine deformities in this group of women regardless the BMD.

High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis.

UNLABELLED Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.

Association Between Lean Mass and Handgrip Strength With Bone Mineral Density in Physically Active Postmenopausal Women

The present study evaluated 117 physically active postmenopausal women (67.8+/-7.0yr) who performed neuromotor physical tests (strength, balance, and mobility). Body composition (lean mass [g], fat mass [g], and % fat) and bone mineral density (BMD) of lumbar spine (L1-L4), femoral neck, and total body were measured by dual-energy X-ray absorptiometry. Following the World Health Organization criteria, osteoporosis was found in at least 1 analyzed site in 33 volunteers (28.2%): 30 (25.6%) in lumbar spine and 9 (7.7%) in femoral neck. Body weight was strongly and positively related to BMD in all sites, but the most important component of body composition was lean mass, also significantly related to all BMD sites, whereas fat mass was weakly related to the femoral neck BMD. Percent fat did not correlate with any BMD site. Of all the physical tests, the handgrip strength was most importantly related to lumbar spine, femoral neck, and total body (r=0.49, p<0.001; r=0.56, p<0.001; and r=0.52, p<0.001, respectively). The static body balance presented a weak but significant positive correlation only with lumbar spine. Our results suggest that strategies aiming to improve muscle strength and lean mass must contribute to the bone health of physically active postmenopausal women.

Circulating Sclerostin in Disorders of Parathyroid Gland Function

CONTEXT Sclerostin, a protein encoded by the SOST gene in osteocytes and an antagonist of the Wnt signaling pathway, is down-regulated by PTH administration. Disorders of parathyroid function are useful clinical settings to study this relationship. OBJECTIVE The objective of the study was to evaluate sclerostin in two different disorders of parathyroid function, primary hyperparathyroidism and hypoparathyroidism, and to analyze the relationship between sclerostin and PTH, bone markers, and bone mineral density. DESIGN This is a cross-sectional study. SETTING The study was conducted at a clinical research center. PATIENTS Twenty hypoparathyroid and 20 hyperparathyroid patients were studied and compared to a reference control group. RESULTS Serum sclerostin was significantly higher in hypoparathyroid subjects than in hyperparathyroid subjects (P < 0.0001) and controls (P < 0.0001). PTH was negatively associated with sclerostin, achieving statistical significance in hypoparathyroidism (r = -0.545; P = 0.02). The bone turnover markers, cross-linked C-telopeptide of type I collagen (CTX) and amino-terminal propeptide of type I collagen (P1NP), were differently associated with sclerostin according to the parathyroid disorder. In primary hyperparathyroidism, bone turnover markers were associated negatively with sclerostin (for P1NP, r = -0.490; P = 0.03). In hypoparathyroidism, bone turnover markers were associated positively with sclerostin (for CTX, r = +0.571; P = 0.01). Although there was no significant correlation between bone mineral density and sclerostin in either parathyroid disorder, there was a significant positive relationship between sclerostin and bone mineral content in hypoparathyroidism. CONCLUSIONS The results are consistent with the hypothesis that PTH is a regulator of sclerostin in human disorders of parathyroid function. In addition, the results suggest that bone mineral content may be another factor that influences sclerostin.

Vitamin D Receptor Gene Polymorphism: Correlation with Bone Mineral Density in a Brazilian Population with Insulin-Dependent Diabetes Mellitus

Abstract: Patients with insulin-dependent diabetes mellitus (IDDM) are at higher risk of developing osteoporosis. Among the genetic factors related to the development of osteoporosis, a possible association between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) has been described in some populations. We characterized the VDR gene polymorphism in a healthy adult Brazilian population and in a group of patients with IDDM and correlated these findings with densitometric values in both groups. The Brazilian population is characterized by an important racial heterogeneity and therefore is considered an ethnically heterogeneous population. We recruited 94 healthy adult Brazilian volunteers (63 women and 31 men), mean (+ SD) age 32.4 + 6.5 years (range 18–49 years), and 78 patients with IDDM (33 women and 45 men) diagnosed before 18 years of age, mean (+ SD) age 23.3 + 5.5 years (range 18–39 years). VDR genotype was assessed by polymerase chain reaction amplification followed by BsmI digestion on DNA isolated from peripheral blood leukocytes. Statistical analysis included Bonferroni t-test to compare densitometric values within different genotypes in both groups and multiple regression analysis of bone density adjusted for potential confounding factors. The IDDM group had a lower BMD compared with the control group. The VDR genotype distribution in the control group was 43 Bb (45.7%), 39 bb (41.5%) and 12 BB (12.8%). This distribution did not differ from that observed in the IDDM group: 39 Bb (50%), 26 bb (33.3%) and 13 BB (16.7%). In the IDDM group, patients with the Bb genotype had a higher body weight when compared with the BB genotype (p= 0.02). However, when diabetic patients were controlled for age, sex and body mass index, BB genotype was associated with a lower mean BMD at lumbar spine and femoral neck than in Bb and bb patients. BB patients had a shorter duration of IDDM than bb and Bb patients. These findings suggest a small influence of VDR gene polymorphism on BMD of a racially heterogeneous population with IDDM.

Relationship between bone mineral density, leptin and insulin concentration in Brazilian obese adolescents

Despite the epidemic of adolescent obesity, the effect of obesity and hormones on bone mineral accrual during growth is poorly understood. Studies using dual-energy X-ray to examine the effect of obesity on bone mass in children and adolescents have yielded conflicting results. The aim of this study was to explore the combined and independent contributions of body mass index, body composition, leptin, insulin, glucose levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) to bone mineral density (BMD) and bone mineral content in a group of Brazilian obese adolescents. This study included 109 post-pubescent obese adolescents. A whole-body dual-energy X-ray absorptiometry scan was performed,using a HOLOGIC QDR4200, to determine whole-body BMD and body composition. Blood samples were collected in the outpatient clinic after an overnight fast, and evaluated for fasting blood glucose and immunoreactive insulin. Leptin levels were assessed with a radioimmunoassay kit. Insulin resistance was assessed by HOMA-IR and the quantitative insulin sensitivity check index. Our results showed that insulin levels and HOMA-IR correlated negatively with BMD and a linear regression analysis showed that serum leptin is inversely associated to BMD adjusted for body mass. In conclusion, our data support the hypothesis that leptin, insulin and HOMA-IR are inversely associated with BMD and play a significant direct role in bone metabolism.

Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta.

Abstract Pamidronate (PAM) infusion is the standard treatment in children with osteogenesis imperfecta (OI). Zoledronic acid (ZOL) is a bisphosphonate with higher potency and faster intravenous infusion, but its efficacy and safety has not been established for OI patients. We report an open-label, prospective, and randomized clinical analysis to study the safety and efficacy of ZOL compared with PAM in 23 children with OI. They were selected to receive PAM (PAM group), 1 mg/kg/day, over 2 days or ZOL (ZOL group), 0.025–0.05 mg/kg/day, over 2 days every 3–4 months according to their ages, during a 1-year follow-up. They were observed for clinical and biochemical parameters, side effects, bone mineral density (BMD), and fracture rate. After treatment, the PAM and ZOL groups average lumbar spine (LS) BMD increased by 51.8% (p=0.053) and 67.6% (p=0.003), respectively. Parallel improvement was seen in LS Z-score in the PAM and ZOL groups, with scores of –5.3 to –3.8 (p=0.032) and –4.8 to –2.3 (p=0.007), respectively. LS Z-score for the ZOL group at the end of treatment was higher compared with the PAM group but only a borderline significance (p=0.053). The total alkaline phosphatase (AP) in the ZOL group significantly decreased from baseline at third and fourth infusion (p=0.032). Mild side effects were similar in both groups, but no severe clinical symptoms were reported. In conclusion, the present study shows that the use of ZOL in the dosage and period studied was safe and efficient to promote a clinical and densitometric improvement, similarly to PAM. Further studies are needed to establish optimal dosing and long-term safety.

Body composition in patients with chronic obstructive pulmonary disease: which method to use in clinical practice?

The objective of the present study was to compare anthropometry with bioelectrical impedance (BIA) in relation to densitometry (dual-energy X-ray absorptiometry; DEXA) as methods of nutritional assessment and body composition in out-patients with chronic pulmonary obstructive disease (COPD). We conducted a cross-sectional clinical study with sixty-one patients with COPD (forty-two men and nineteen women), mean age of 66.5 (sd 7.9) years and forced expiratory volume in 1 s of 1.3 (sd 0.6) litres (52.2 (sd 19.8) % predicted), referred to the Pulmonary Rehabilitation Center. The patients were evaluated regarding nutrition status and body composition as determined by anthropometry, BIA and DEXA. In the results, 34.4 % showed mild obstruction, 31.2 %, moderate and 34.4 %, severe obstruction. According to the BMI (mean 24.5 (sd 4.5) kg/m2), 45.9 % of the patients exhibited normal weight, while 27.9 % were underweight and 26.2 % were obese. Related to fat-free mass (FFM), anthropometry and BIA compared with DEXA presented high correlations (r 0.96 and 0.95 respectively; P < 0.001) and high reliability between the methods (alpha 0.98; P < 0.001). Agreement analysis between the methods shows that anthropometry overestimates (0.62 (sd of the difference 2.89) kg) while BIA underestimates FFM (0.61 (sd of the difference 2.82) kg) compared with DEXA. We concluded that according to the nutritional diagnosis, half of our population of patients with COPD showed normal weight, while the other half comprised equal parts obese and underweight patients. Body composition estimated by BIA and anthropometry presented good reliability and correlation with DEXA; the three methods presented satisfactory clinical accuracy despite the great disparity of the limits of agreement.