Pedro Henrique Silveira Corrêa

Brazilian normal static bone histomorphometry: effects of age, sex, and race

Bone histomorphometry values for normal individuals within different populations have been well established. We studied iliac crest bone samples from 125 healthy Brazilian subjects. The effect of sex, race, and age variables on histomorphometric parameters was evaluated. Bone volume showed a trend to decrease with age in both sexes, being significantly higher in black females and Caucasian males. Interactions among sex, race, and age had no effect on trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). However, age had a significant effect on Tb.Th and Tb.Sp, and sex had an impact on Tb.Sp. Trabecular number (Tb.N) was higher in black females than in males and was higher in Asian males than in females. Among females, Tb.N was lower in Asians than in other races and was higher in blacks than in Caucasians and or in those of mulattos. In addition, Tb.N was higher in males under 10 than in males over 50 years old, was higher in females under 10 than in females in any other age bracket, and was lower in females in the 41–50 age bracket than in younger females. Osteoid volume and osteoid surface were significantly higher in males than in females, and a significant age-related difference in osteoid thickness was observed. No significant sex-related or race-related differences were found in terms of resorption, although eroded surface decreased with age. In conclusion, sex, race, and age, as well as interactions among these three variables, were found to affect some static histomorphometric indexes in healthy Brazilian subjects.

Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1.

Objective  To characterize clinical features and identify MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1 (MEN1).

Improvement of adynamic bone disease after renal transplantation

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Bone histomorphometry in Cushing's syndrome

Bone involvement is a common finding in Cushing’s syndrome. The actions of corticosteroids on bone have been studied quite intensively but only a few studies of bone histomorphometry in this syndrome have been published. In this paper we present histomorphometric measurements of bone activity in 7 patients with a postoperative reevaluation in two. The results show irregular alterations on histomorphometric parameters with an increased bone resorption and decreased bone formation rate. After surgery the abnormalities changed towards normal.

Potential effects of alendronate on fibroblast growth factor 23 levels and effective control of hypercalciuria in an adult with Jansen's metaphyseal chondrodysplasia.

CONTEXT Jansens metaphyseal chondrodysplasia (JMC) is a rare autosomal dominant disorder caused by activating mutations in the PTH 1 receptor (PTH1R; PTH/PTHrP receptor), leading to chronic hypercalcemia and hypercalciuria. Hypophosphatemia is also a hallmark of JMC, and recently, increased fibroblast growth factor 23 (FGF23) levels have been reported in this syndrome. Hypercalcemia has been associated with increased cardiovascular risk; however, cardiovascular disease has not been extensively investigated in JMC patients. OBJECTIVE The aim of the study was to describe the long-term follow-up of a JMC patient with regard to the management of hypercalciuria, the evaluation of FGF23 levels under bisphosphonate treatment, and the investigation of cardiovascular repercussion of chronic hypercalcemia. RESULTS The diagnosis of JCM was confirmed by molecular analysis (p.H223R mutation in PTH1R). The patient was followed from 5 to 27 yr of age. Asymptomatic nephrolithiasis was diagnosed at 18 yr of age, prompting pharmacological management of hypercalciuria. Treatment with alendronate reduced hypercalciuria; however, normocalciuria was only obtained with the association of thiazide diuretic. Serum FGF23 levels, measured under alendronate treatment, were repeatedly within the normal range. Subclinical cardiovascular disease was investigated when the patient was 26 yr old, after 19 yr of sustained mild hypercalcemia; carotid and vertebral artery ultrasonography was normal, as well as coronary computed tomography angiography (calcium score = 0). CONCLUSION The long-term follow-up of our JMC patient has provided insight on therapeutic strategies to control hypercalciuria, on the potential effects of alendronate on FGF23 levels, and on the lack of detectable cardiovascular disease at young adulthood after prolonged exposure to hypercalcemia.

New mutation in the CASR gene in a family with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT)

A loss of calcium-sensing receptor (CASR) function due to inactivating mutations can cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). NSHPT represents the most severe expression of FHH and courses as a life-threatening condition. The aim of this study was to identify and characterize a CASR mutation in a female infant brought to the health service due to dehydration, apathy, lack of breast feeding and severe hypercalcemia. Molecular analysis was performed on genomic DNA of the index case and her parents. A novel homozygous mutation (p.E519X) in CASR was identified in the proband; both mother and father had the same mutation in heterozygous state, confirming their FHH condition. The mutation results in a truncated and inactive protein due to the lack of transmembrane and intracellular domains. The identification of this novel CASR gene mutation established the basis of hypercalcemia in this family and allowed a genetic counseling.

Renal failure after surgery for primary hyperparathyroidism: is acute reduction of parathyroid function a risk factor?

A possible deleterious effect of parathyroidectomy on renal allograft function has been discussed in recent literature.1 Schwarz et al. observed a correlation between acute kidney dysfunction and the degree of parathyroid hormone (PTH) reduction following a parathyroidectomy for tertiary hyperparathyroidism (HPT).2 This effect seems to be in contrast to some physiological studies demonstrating that injection of PTH is associated with a reduction in the glomerular capillary ultrafiltration coefficient (Kf).3 Based on this evidence, the acute reduction in PTH would theoretically improve glomerular filtration. In general, the reversal of HPT would prevent further renal damage. Stable or improved renal function are the observed clinical courses for most patients in the long-run, but we observed a different pattern during the first 48 hours after the operation, with a transitory increase in creatinine levels above 10% in 77 of 105 patients after parathyroidectomy for primary HPT.4 Creatinine levels increased more than 50% in 18 patients (17.1%).4 In renal stone patients, a slight increase in creatinine after successful resection of a parathyroid adenoma was recently commented5. The elevation of creatinine was transient and clinically silent in most of our patients. However, acute deterioration of renal function requiring dialysis occurred in two of 183 (1.1%) patients with primary HPT who underwent surgery from 1997 to 2007. The outcome of these cases may indicate a potentially relevant role of the parathyroid glands in renal regulation.

An Architecture for Integrating Databases with Replication Support Based on the OGSA-DAI Middleware

In recent years, Grid Computing has become a key technologyin resource integration and sharing, thus improvingscientific collaboration among different institutions. Whilesome applications need access databases spread across theparticipants of the grid, OGSA-DAI is middleware that enablesdatabase integration and sharing from different vendors.By using replication techniques, this work aims toprovide a higher level of availability and reliability whenusing databases exposed to the grid. It defines an architecturefor systems that want to offer replication to the grid andwe implemented extensions to the OGSA-DAI middlewarein order to achieve this objective and prove the concepts ofthe proposed architecture. This paper presents the resultsobtained in the implementation and an initial study of itsapplication in a Health Care Information System.

Concordance Between Whole-Body Scintigraphy 111In-Octreotide and 99mTc-Sestamibi Uptake in the Detection of Four Tumor-Induced Osteomalacia Cases

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumors secrete phosphaturic factors such as fibroblast growth factor-23, which increases renal phosphate excretion, causing hypophosphatemia and osteomalacia. These tumors have mesenchymal origin and are usually small and slow growing, and they can be located anywhere in the body. Because the cure for TIO includes its total resection, the challenge of the treatment is to locate it (1). Once TIOs express somatostatin receptor subtypes 2 and 5, In-octreotide (especially if combined with SPECT/CT [single photon emission computed tomography/computed tomography]) and more recently Ga-DOTANOC PET/CT (positron emission tomography/CT) and Ga-DOTATATE PET/CT have been shown to be excellent in their detection (2). Because TIOs are highly vascular, Tc-sestamibi scintigraphy (MIBI) has also been used for this purpose (3–5). We follow four patients (three women and one man; ages 12–46 y) whose clinical picture and laboratorial data suggested hypophosphatemic osteomalacia, which was confirmed by bone histomorphometry. They underwent whole-body scintigraphy In-Octreotide (Octreoscan) and Tcsestamibi to localize the tumor. Both methods revealed that the same body areas of focally increased tracer uptake in different anatomical sites in each patient (right leg, left foot, left leg, and left knee) were visualized in detail with magnetic resonance image (Figure 1). Histopathological findings after the tumor’s resection confirmed the existence of phosphaturic mesenchymal tumor, a mixed connective tissue variant. In these four patients, both methods (whole-body scintigraphy In-octreotide and MIBI) detected TIOs. For this reason, when Octreoscan is not available, we encourage TIO screening by MIBI.

Relato de caso: doença celíaca recém-diagnosticada como fator agravante de osteoporose em mulher idosa

Sixty-three-year-old woman requested medical attention for osteoporosis. Bone densitometry revealed: Tspine (L1-L4)= -3.5 SD [Bone mineral density (BMD): 0.766 g/cm2]. Tfemoral neck= -2.4 SD (BMD: 0.716 g/cm2). She has been in calcium and vitamin D supplementation for 2 years. She informed a 5-year-history of hypothyroidism in levothyroxine replacement. Alendronate sodium 70 mg/week was initiated with significant increase in BMD in the first year (6.1% equally in spine and femoral neck). After a 5-year follow-up, the patient presented with weight loss, anemia and decrease in BMD (12.6% in spine and 20.9% in femoral neck). Clinical history revealed intermittent diarrhea episodes for 2 years and the hypothesis of celiac disease was suspected. Anti-gliadin and anti-endomysium antibodies were positive: 25.3 U/mL (< 20) e 1/5 U/mL (RV: negative), respectively. Bone biochemical parameters revealed normal levels of calcium and phosphate, increased parathyroid hormone: 283 pg/mL (10-65) and increased levels of bone reabsortion markers, consistent with secondary hyperparathyroidism in response to malabsorptive syndrome. One year after gluten-free diet, patient improved of malabsorptive symptoms and gained BMD (47.3% in spine and 31.6% in femoral neck), confirming the hypothesis of celiac disease as aggravating factor of osteoporosis in this patient.