Early-Onset, Progressive, Frequent, Extensive, and Severe Bone Mineral and Renal Complications in Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism

Differences in bone mineral density (BMD) patterns have been recently reported between multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) and sporadic primary HPT However studies on the early and later outcomes of bone/renal complications in HPT/MEN1 are lacking In this cross sectional study performed in a tertiary academic hospital 36 patients cases with uncontrolled HPT from 8 unrelated MEN1 families underwent dual energy X ray absorptiometry (DXA) scanning of the proximal one third of the distal radius (1/3DR) femoral neck, total hip, and lumbar spine (LS) The mean age of the patients was 389 +/- 145 years Parathyroid hormone (PTH)/calcium values were mildly elevated despite an overall high percentage of bone demineralization (77 8%) In the younger group (<50 years of age) demineralization in the 1/3DR was more frequent more severe and occurred earlier (40% Z-score 1 81 +/- 0 26) The older group (>50 years of age) had a higher frequency of bone demineralization at all sites (p < 005) and a larger number of affected bone sites (p < 0001), and BMD was more severely compromised in the 1/3DR (p = 007) and LS (p= 002) BMD values were lower in symptomatic (88 9%) than in asymptomatic HPT patients (p < 006) Patients with long standing HPT (>10 years) and gastnnoma/HPT presented significantly lower 1/3DR BMD values Urolithiasis occurred earlier (<30 years) and more frequently (75%) and was associated with related renal comorbidities (50%) and renal insufficiency in the older group (33%) Bone mineral- and urolithiasis-related renal complications in HPT/MEN1 are early onset frequent extensive severe and progressive These data should be considered in the individualized clinical/surgical management of patients with MEN1 associated HPT (C) 2010 American Society for Bone and Mineral Research

Characterization of Adult Stem/Progenitor Cell Populations From Bone Marrow in a Three-Dimensional Collagen Gel Culture System.

Stem cell transplantation therapy using mesenchymal stem cells (MSCs) is considered a useful strategy. Although MSCs are commonly isolated by exploiting their plastic adherence, several studies have suggested that there are other populations of stem and/or osteoprogenitor cells which are removed from primary culture during media replacement. Therefore, we developed a three-dimensional (3D) culture system in which adherent and non-adherent stem cells are selected and expanded. Here, we described the characterization of 3D culture-derived cell populations in vitro and the capacity of these cells to differentiate into bone and/or cartilage tissue when placed inside of demineralized bone matrix (DBM) cylinders, implanted subcutaneously into the backs of rat for 2, 4 and 8 weeks. Our results demonstrates that 3D culture cells were a heterogeneous population of uncommitted cells that express pluripotent, hematopoietic, mesenchymal and endothelial specific markers in vitro and can undergo osteogenic differentiation in vivo.

Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.

Avaliação das metaloproteinases de matriz -2 e -9 em gatos com desmineralização óssea secundária à tirotoxicose induzida

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Densitometria óptica radiográfica na avaliação do hiperparatireoidismo secundário nutricional induzido em gatos jovens

O trabalho teve por objetivos verificar as alterações da densidade mineral óssea e as alterações bioquímicas, no hiperparatireoidismo secundário nutricional. Foram utilizados 10 gatos, sem raça definida, com idade inicial entre 2 e 3 meses e peso médio de 820 gramas. Após um período de adaptação de 10 dias, eles foram submetidos a uma dieta composta por coração bovino moído e cru durante 60 dias, sendo os exames efetuados no final do período de adaptação e a cada 15 dias. Empregou-se o método de densitometria óptica em imagens radiográficas, do rádio e ulna direitos. Não foi observada diferença estatística na densidade mineral óssea entre o final do período de adaptação e com 15 dias de alimentação com carne de coração. Aos 30 dias, houve uma diminuição significante estatisticamente, que se manteve no mesmo patamar aos 45 e 60 dias. em nenhum momento de observação ocorreu diferença estatística nos níveis séricos de cálcio e fósforo. Os níveis séricos de fosfatase alcalina variaram e estavam acima dos valores normais no 45º e 60º dia da dieta. Foi possível concluir que a densitometria óptica em imagens radiográficas é um método eficiente de avaliação da desmineralização óssea, ao passo que as análises bioquímicas séricas de cálcio, fósforo e fosfatase alcalina são de valor limitado.

Histomorphometric analysis of homogenous demineralized dentin matrix as osteopromotive material in rabbit mandibles

Purpose: The aim of this work was to evaluate the effectiveness of homogenous demineralized dentin matrix (HDDM) slices in surgical bone defects created in the mandibles of rabbits and occluded with a polytetrafluoroethylene (PTFE) membrane in the promotion of bone growth. Materials and Methods: Surgical bone defects were created in 36 adult rabbits and divided into 4 groups: bone defect (control), bone defect with PTFE membrane, bone defect with HDDM, and bone defect with both HDDM and a PTFE membrane (HDDM + PTFE). The rabbits were sacrificed after 30, 60, and 90 days, and the bone defects were examined histologically and by histomorphometric analysis (analysis of variance and the Tukey test). Results: The volume of newly formed bone matrix was significantly greater in the HDDM and HDDM + PTFE groups than in the control and PTFE groups. The discrete inflammatory reaction found in the HDDM and HDDM + PTFE groups did not prevent the osteopromotive activity of the dentin matrix. Discussion: HDDM slices were biocompatible and were resorbed during the bone remodeling process. They stimulated the newly formed bone until 30 days after implantation. Conclusion: Bone repair was accelerated in the bone defects treated with HDDM in comparison to the control group.

Determinação de desmineralização óssea em gatos após tirotoxicose experimental

Hyperthyroidism can result in serious effects on the bone metabolism in humans as well as animals. For a better characterization of thyrotoxicosis effects, 16 cats were induced into thyrotoxicosis by intaking a dose of 150 μg/kg of sodium L-thyroxine every 24 hours during 42 days. The hormonal levels were evaluated by radioimmunoassay technique and the bone mineral density of the right distal radius extremity was measured through the radiographic optical densitometry. Was verified significant bone demineralization seven days of hormonal intake as weel as radius demineralization.

Correlação entre a densidade mineral óssea e níveis séricos de cálcio, fósforo e fosfatase alcalina total em gatos após tirotoxicose experimental

Hyperthyroidism is and endocrinal dysfunction characterized by excessive serum concentrations of thyroid gland hormones, which can cause several effects on the bone tissue in humans and in animals. For a better characterization of thyrotoxicosis effects on bone metabolism, 16 cats were induced into hyperthyroid state. Results showed that, in some moments a major bone demineralization of the right distal radium estremity promoted an elevation of the serum levels of phosphorus and total alkaline phosphatase.

Treatment of gingival recession with collagen membrane and DFDBA: A histometric study in dogs

In a previous study, we evaluated the findings related to the use of resorbable collagen membranes in humans along with DFDBA (demineralized freeze-dried bone allograft). The aim of this subsequent study was to histometrically evaluate in dogs, the healing response of gingival recessions treated with collagen membrane + DFDBA (Guided Tissue Regeneration, GTR) compared to a coronally positioned flap (CPF). Two types of treatment were randomly carried out in a split-mouth study. Group 1 was considered as test (GTR: collagen membrane + DFDBA), whereas Group 2 stood for the control (only CPF). The dogs were given chemical bacterial plaque control with 0.2% chlorhexidine digluconate during a 90-day repair period. Afterwards, the animals were killed to obtain biopsies and histometric evaluation of the process of cementum and bone formation, epithelial migration and gingival level. A statistically significant difference was found between groups with a larger extension of neoformed cementum (GTR = 32.72%; CPF = 18.82%; p = 0.0004), new bone (GTR = 23.20%; CPF = 09.90%; p = 0.0401) and with a smaller area of residual gingival recession in the test group (GTR = 50.69%; CPF = 59.73%; p = 0.0055) compared to the control group. The only item assessed that showed no statistical difference was epithelial proliferation on the root surface, with means of 15.14% for the GTR group and 20.34% for the CPF group (p = 0.0890). Within the limits of this study we concluded that the treatment of gingival recession defects with GTR, associating collagen membrane with DFDBA, showed better outcomes in terms of a larger extension of neoformed cementum and bone, as well as in terms of a smaller proportion of residual recessions.

Increased apoptosis in osteoclasts and decreased RANKL immunoexpression in periodontium of cimetidine-treated rats

It has been demonstrated that histamine interferes with the recruitment, formation and activity of osteoclasts via H1- and H2-receptors. Cimetidine is a H2-receptor antagonist used for treatment of gastric ulcers that seems to prevent bone resorption. In this study, a possible cimetidine interference was investigated in the number of alveolar bone osteoclasts. The incidence of osteoclast apoptosis and immunoexpression of RANKL (receptor activator of nuclear factor κB ligand) was also evaluated. Adult male rats were treated with 100mg kg-1 of cimetidine for 50days (CimG); the sham group (SG) received saline. Maxillary fragments containing the first molars and alveolar bone were fixed, decalcified and embedded in paraffin. The sections were stained by H&E or submitted to tartrate-resistant acid phosphatase (TRAP) method. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) method and immunohistochemical reactions for detecting caspase-3 and RANKL were performed. The number of TRAP-positive osteoclasts, the frequency of apoptotic osteoclasts and the numerical density of RANKL-positive cells were obtained. Osteoclast death by apoptosis was confirmed by transmission electron microscopy (TEM). In CimG, TRAP-positive osteoclasts with TUNEL-positive nuclei and caspase-3-immunolabeled osteoclasts were found. A significant reduction in the number of TRAP-positive osteoclasts and a high frequency of apoptotic osteoclasts were observed in CimG. Under TEM, detached osteoclasts from the bone surface showed typical features of apoptosis. Moreover, a significant reduction in the numerical density of RANKL-positive cells was observed in CimG. The significant reduction in the number of osteoclasts may be due to cimetidine-induced osteoclast apoptosis. However, RANKL immunoexpression reduction also suggests a possible interference of cimetidine treatment in the osteoclastogenesis. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

Perfil metabólico de cálcio e ósseo de pacientes soropositivos para HIV em uso ou não da terapia antirretroviral

Pós-graduação em Alimentos e Nutrição - FCFAR

Tirotoxicose experimental em gatos: efeitos sobre o tecido ósseo, isoenzimas da fosfatase alcalina e metaloproteínases de Matriz-2 E-9

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Progression of steroid-associated osteoporosis after heart transplantation

BACKGROUND: Osteoporosis has been recognized as an important side effect of long-term and of pulsed steroid application after heart transplantation. METHODS: In June 1989 a prospective clinical trial was started to study bone demineralization by quantitative computed tomographic scan. All patients received vitamin D and calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council Standard Units subcutaneously per day was administered in 14-day cycles, whereas group II patients (n = 31) received a placebo preparation. Repeat trabecular and cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation. RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months in the calcitonin group. The values for cortical bone density decreased significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart transplantation. Comparable results were obtained in the placebo group. In both groups bone density remained stable thereafter. Intergroup differences were not of statistical significance. CONCLUSIONS: In heart transplant recipients progressive trabecular bone demineralization is limited to the first 3 postoperative months. Thereafter, bone density remained stable. A positive effect of synthetic calcitonin in addition to prophylactic calcium and vitamin D application could not be proved by repeat quantitative computed tomography.

No evidence of osteopenia 5 to 8 years after ileal orthotopic bladder substitution

The use of bowel segments as bladder substitutes may result in chronic, impaired vitamin D and calcium metabolism, and ultimately in bone demineralization.

The health and nutritional status of multiethnic perimenopausal women

An integrated, dual-phase study design assessed the health and nutritional status and practices of African-American (A-A), Caribbean (A-C), and white non-Hispanic (W-A) women during perimenopause (40–55 years). During Phase I, four focus groups (n = 37) of male and female participants discussed the health and social implications of perimenopause. A conceptual framework for the main study (Phase II) was developed from the focus groups' findings, in concert with the main study's specific aims and objectives. ^ The main study, a cross-sectional survey, quantitatively assessed the health and nutritional status of a convenience sample of 109 women (25 A-A, 31 A-C and 53 W-A), who met specific eligibility criteria. Using seven instruments, sociodemographic, dietary, medical, reproductive health, health practice and anthropometric data were collected. ^ The groups were of comparable age, education, and socioeconomic status (SES). Despite these similarities, statistically significant interethnic nutritional status differences were found. Significantly more total energy and energy from fat were consumed by A-A than W-A and A-C women. Also, significantly more A-A and A-C than W-A women were overweight or obese with android-type weight patterning. ^ Overall, iron and calcium Recommended Dietary Allowances (RDA's) were not met by 35% and 68% of participants, respectively. Iron deficiency anemia was reported by 29% of participants while 33% reported heavier menstrual bleeding. Coupled with suboptimal iron intakes, this is likely to present a serious public health problem. Similarly, increased bone demineralization characteristic of perimenopause, coupled with suboptimal calcium intakes could precipitate another public health problem, osteoporosis. ^ Participants had different expectations about the role of medical care during perimenopause. Significantly more white (57%) than black (38% [A-A and AC]) women sought medical attention for symptoms. Whereas Hormone Replacement Therapy (HRT) was prescribed for 25% of them, only 13% were compliant at enrollment. ^ The trends and statistically significant findings of this study have huge public health policy implications. It is imperative that appropriate policies are formulated to ensure that America's ethnically diverse perimenopausal women have ready access to culturally appropriate care. This would optimize their health outcomes, and enhance their quality of life and productive capacities at this critical juncture of their lives. ^