How does women's bone health recover after lactation? A systematic review and meta-analysis.

This is a systematic review aiming to evaluate the recovery of bone mass after lactation-related loss. Bone loss is transitory with recovery depending on the return of menstruation and weaning, and several compensatory homeostatic mechanisms are involved to minimize any significant damage to the maternal skeleton. Lactation has been associated with significant temporary bone loss, especially during the exclusive breastfeeding period. In the bone recovery phase, there is wide methodological heterogeneity among clinical trials, including follow-up timing, methods and sites of bone measurements, and body composition changes. The purpose of this study is to perform a systematic review and meta-analysis aiming to evaluate the recovery rate of bone mass after lactation-related loss, including the PubMed, Web of Science, and Scopus databases, with no publication date restrictions. The following MeSH terms were used: "bone diseases," "bone resorption," "bone density," "osteoporosis," "calcium," "postpartum period," "weaning," "breast feeding," and "lactation." The inclusion criteria were as follows: prospective human studies in women of reproductive age and bone measurements with two assessments in the postpartum period at least: the first one within the first weeks of lactation and another one 12 months after delivery, 3 months following the return of menses or 3 months postweaning. This research was recorded on the Prospero database (CRD42018096586Bone). A total of 9455 studies were found and 32 papers met the inclusion criteria. The follow-up period ranged from one to 3.6 years postpartum. Lactation was associated with transient bone loss, with a strong tendency to recover in all the sites studied, depending on the return of menstruation and weaning. Small deficits in the microarchitecture of the peripheral skeleton may be present, especially in women with prolonged breastfeeding, but with no deficit regarding the hip geometry was found. Women with a successive gestation after prolonged lactation and women who had breastfed when adolescents had no significant bone loss. Bone loss related to lactation is transitory, and several compensatory homeostatic mechanisms are involved to minimize any significant damage to the maternal skeleton.

Increased rate of osteoporosis, low lean mass, and fragility fractures in COPD patients: association with disease severity.

A very high rate of osteoporosis, fractures, and low lean mass was observed in patients with chronic obstructive pulmonary disease (COPD). Disease severity was associated with bone and muscle adverse outcomes, while age ≥ 63.5 years old, low lean mass, higher iPTH, and a T-score below - 2.5 were all associated with higher risk of fracture. INTRODUCTION: Osteoporosis is frequently neglected in patients with COPD. We aimed at evaluating the rate of osteoporosis, fractures, and low lean mass in patients with COPD. METHODS: Ninety-nine patients with COPD (53 women, 64.5 ± 9.6 years old, and 46 men, 65.9 ± 8.0 years old) underwent bone densitometry (DXA) with body composition analyses. Healthy individuals (N = 57) not exposed to tobacco matched by sex, age, and body mass index (BMI) were used as controls. Spirometry, routine laboratory workout, and conventional thoracolumbar radiography surveying for vertebral deformities were performed in all patients. RESULTS: Osteoporosis was found in 40.4% of the COPD patients against only 13.0% of the healthy controls (p = 0.001). Vertebral fractures were seen in 24.4% of the men and 22.0% of the women with COPD. Disease severity (GOLD 3 and 4) was significantly associated with higher risk of vitamin D deficiency (p = 0.032), lower BMD (both men and women at all sites), higher frequency of osteoporosis (in women at all sites), lower skeletal mass index, and higher rate of low lean mass (in both men and women) than healthy controls and COPD patients with milder disease (GOLD 1 and 2). Age was a main predictor of vertebral fractures (OR = 1.164 (1.078-9.297); p < 0.001), while high plasma iPTH (OR = 1.045 (1.005-1.088); p = 0.029) and low ALM (OR = 0.99965 (0.99933-0.99997); p = 0.031) were predictors of non-vertebral fractures. CONCLUSION: Highly prevalent in COPD, osteoporosis and low lean mass were associated with FEV1% < 50%. Age, low lean mass, high iPTH, and low bone mass were all significantly associated with fractures in COPD patients.

Development and validation of a tool for identifying women with low bone mineral density and low-impact fractures: the São Paulo Osteoporosis Risk Index (SAPORI).

UNLABELLED: The performance of the São Paulo Osteoporosis Risk Index (SAPORI) was tested in 1,915 women from the original cohort, São Paulo Osteoporosis Study (SAPOS) (N = 4332). This new tool was able to identify women with low bone density (spine and hip) and low-impact fracture, with an area under the receiving operator curve (ROC) of 0.831, 0.724, and 0.689, respectively. INTRODUCTION: A number of studies have demonstrated the clinical relevance of risk factors for identifying individuals at risk of fracture (Fx) and osteoporosis (OP). The SAPOS is an epidemiological study for the assessment of risk factors for Fx and low bone density in women from the community of the metropolitan area of São Paulo, Brazil. The aim of the present study was to develop and validate a tool for identifying women at higher risk for OP and low-impact Fx. METHODS: A total of 4,332 pre-, peri-, and postmenopausal women were analyzed through a questionnaire addressing risk factors for OP and Fx. All of them performed bone densitometry at the lumbar spine and proximal femur (DPX NT, GE-Lunar). Following the identification of the main risk factors for OP and Fx through multivariate and logistic regression, respectively, the SAPORI was designed and subsequently validated on a second cohort of 1,915 women from the metropolitan community of São Paulo. The performance of this tool was assessed through ROC analysis. RESULTS: The main and significant risk factors associated with low bone density and low-impact Fx were low body weight, advanced age, Caucasian ethnicity, family history of hip Fx, current smoking, and chronic use of glucocorticosteroids. Hormonal replacement therapy and regular physical activity in the previous year played a protective role (p < 0.05). After the statistical adjustments, the SAPORI was able to identify women with low bone density (T-score ≤ -2 standard deviations) in the femur, with 91.4% sensitivity, 52% specificity, and an area under the ROC of 0.831 (p < 0.001). At the lumbar spine, the performance was similar (81.5% sensitivity, 50% specificity, and area under ROC of 0.724; p < 0.001). Regarding the identification of low-impact Fx, the sensitivity was 71%, the specificity was 52%, and the area under the ROC was 0.689 (p < 0.001). CONCLUSION: The SAPORI is a simple, useful, fast, practice, and valid tool for identifying women at higher risk for low bone density and osteoporotic fractures.

Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

Low-trauma ankle fractures in Brazil: secular trends in patients over 50 years old from 2004 to 2013.

PURPOSE: The most common sites of low-energy trauma fractures are the femur, vertebra, humerus, and forearm. Ankle fractures have significant morbidity and high costs for surgical procedure. Forearm fractures are common nonvertebral fractures. Forearm fractures are classified as fragility fractures and predictive for fractures at other sites, although do not allow osteoporosis diagnosis. It is controversial whether ankle fractures are osteoporosis fractures. METHODS: Retrospective observational study, with secular trend analysis, in patients over 50 years old admitted in the Brazilian Public Health System, from 2004 to 2013. We collected hospitalization data according to the ICD-10 for low-trauma ankle and forearm fractures. Fracture rate was calculated according to gender, age, and geographic region, performed linear regression analysis, and estimated fracture rates for 2030. Comparison of ankle and forearm rates was also performed, grouping them in 3-year block. ANOVA test was used to compare each block. RESULTS: Ankle fracture rate was 21.39 fractures per 100,000 inhabitants, 23.98 in females and 18.49 in males. Fracture rates were higher in the South and Southeast regions. In absolute numbers, although ankle fracture rate increased with age, there was a significant decrease in the population over 80 years old. Data showed stabilization in ankle fractures from 2004 to 2013, in women and men. In 3-year block analysis, men had higher ankle fracture rates than forearm. However, in women, forearm rates were higher than ankle. CONCLUSION: Our data suggest that ankle fractures in men would be considered as a sentinel fracture with a similar clinical impact of forearm fracture.

A bone remodeling model governed by cellular micromechanics and physiologically based pharmacokinetics.

This study describes a mathematical model for bone remodeling that integrates the bone cells activities with the pharmacological dynamics for bone-seeking agents. The evolution of bone cells population involves the osteoblast-osteoclast signaling mediated by biochemical factors and receives both mechanical stimulus evaluated at the microscale and pharmacological regulation. A physiologically based pharmacokinetic model (PBPK) for bone-seeking agents was developed to provide the drug concentration on bone sites and feed the remodeling algorithm. The drug effect on bone was reproduced coupling three different strategies: modification of the RANKL expression, increase the osteoclast apoptosis and change in the rate of differentiation of preosteoblasts. Computational simulations were performed in the PBPK model considering different dosing regimens. A 3D finite element model of a proximal femur was generated and the simulation of the bone remodeling algorithm were implemented in Matlab. The results indicate that the proposed integrated model is able to capture adequately the expected adaptive behavior of bone subjected to mechanical and pharmacological stimulus. The model demonstrated to have potential for use as a platform to investigate therapies and may help in the study of new drugs for bone diseases.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS).

UNLABELLED: The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. INTRODUCTION: The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. METHODS: A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. RESULTS: The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). CONCLUSION: Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.

Validation of a food frequency questionnaire for women with osteoporosis.

The importance of nutrient intakes in osteoporosis prevention in treatment is widely recognized. The objective of the present study was to develop and validate a FFQ for women with osteoporosis. The questionnaire was composed of 60 items, separated into 10 groups. The relative validation was accomplished through comparison of the 3-Day Food Record (3DR) with the FFQ. The 3DR was applied to 30 elderly women with confirmed osteoporosis, and after 45 days the FFQ was administrated. Statistical analysis comprised the Kolmogorov-Smirnov, Student T test and Pearson correlation coefficient. The agreement between two methods was evaluated by the frequency of similar classification into quartiles, and by the Bland-Altman method. No significant differences between methods were observed for the mean evaluated nutrients, except for carbohydrate and magnesium. Pearson correlation coefficients were positive and statistically significant for all nutrients. The overall proportion of subjects classified in the same quartile by the two methods was on average 50.01% and in the opposite quartile 0.47%. For calcium intake, only 3% of subjects were classified in opposite extreme quartiles by the two methods. The Bland-Altman analysis demonstrated that the differences obtained by the two methods in each subject were well distributed around the mean of the difference, and the disagreement increases as the mean intake increases. These results indicates that the FFQ for elderly women with osteoporosis presented here is highly acceptable and is an accurate method that can be used in large-scale or clinical studies for evaluation of nutrient intakes in a similar population.

Prevalence of low trauma fractures in long-term kidney transplant patients with preserved renal function.

We evaluated the prevalence of low bone mineral density (BMD) and osteoporotic fractures in kidney transplantation (KT) patients and determined risk factors associated with osteoporotic fractures. The study was conducted on 191 patients (94 men and 97 women) with first KT for 3 years or more presenting stable and preserved renal function (serum creatinine levels lower than 2.5 mg/dl). KT patients were on immunosuppressive therapy and the cumulative doses of these drugs were also evaluated. BMD was determined by dual-energy X-ray absorptiometry at multiple sites (spine, femur and total body). Quantitative ultrasound of the calcaneus (broadband ultrasound attenuation, speed of sound, and stiffness index, SI) was also performed. Twenty-four percent (46) of all patients had either vertebral (29/46) or appendicular (17/46) fractures. We found osteoporosis and osteopenia in 8.5-13.4 and 30.9-35.1% of KT patients, respectively. Women had more fractures than men. In women, prevalent fractures were associated with diabetes mellitus [OR = 11.5, 95% CI (2.4-55.7)], time since menopause [OR = 3.7, 95% CI (1.2-11.9)], femoral neck BMD [OR = 1.99, 95% CI (1.4-2.8)], cumulative dose of steroids [OR = 1.1, 95% CI (1.02-1.12)] and low SI [OR = 1.1, 95% CI (1.0-1.2)]. In men, fractures were associated with lower lumbar spine BMD [OR = 1.75, 95% CI (1.1-2.7)], lower SI [OR = 1.1, 95% CI (1.03-1.13)], duration of dialysis [OR = 1.3, 95% CI (1.13-2.7)], and lower body mass index [OR = 1.24, 95% CI (1.1-1.4). Our results demonstrate high prevalence of low BMD and osteoporotic fractures in patients receiving a successful kidney transplant and indicate the need for specific intervention to prevent osteoporosis in this population.

[Subclinical apoplexy in pituitary tumors]. / Apoplexia subclínica em tumores pituitários.

Acute pituitary apoplexy is a rare event, even in patients with pituitary macroadenomas. On the other hand, the presence of necrotic/hemorrhagic areas, especially in macroadenomas, seems to be more common than earlier reported in the CT period. After the introduction of MR in the presurgical workup of these patients, these apopleptic areas have been more easily diagnosed preoperatively. Forty consecutive patients with pituitary macroadenomas were studied with high-resolution 1.5 T T1 coronal, sagittal and axial slices over the sellar region. Special attention was paid in the detection of necrotic, cystic and hemorrhagic areas within these tumors. Ten patients had hemorrhagic/necrotic areas within their tumors, without any sign or symptom of acute apoplexy. These areas varied from small (2 mm) to very large (30 mm) ones. Seven patients had non-secreting tumors, 2 GH and 1 prolactin secreting tumors, which is the same profile of secretory pattern for the whole series (40 patients). The clinical picture included (other than that caused by endocrine secretion) slowly progressive (but not acute) visual loss (n = 8) and headache (n = 3). After surgical decompression of the surrounding structures and visual apparatus, which was facilitated by the presence of the necrotic areas, there was visual improvement in 6 patients and headache resolution in 2. The presence of asymptomatic apopletic areas in these macroadenomas and their absence in microadenomas as can be seen in the literature suggest that they are related more to the size of the tumor than to its endocrine secretion pattern. This is in agreement with a vascular insufficiency hypothesis in the pathogenesis of these lesions.

[Identical twins discordant for Cushing's disease: case report[]. / Gêmeas idênticas discordantes para a doença de Cushing. Relato de caso.

Cushing's disease is rare in children and its occurrence in identical twins is extremely rare. This paper reports on identical twins discordant for Cushing's disease. One of them first presented with a cushingoid phenotype by the age of 10. Her evaluation showed an increased urinary free-cortisol and serum ACTH. Her pattern in the dexametazone suppression tests was compatible with Cushing's disease. MRI disclosed a pituitary macroadenoma which was removed by the transesphenoidal approach. Immunohistochemical studies of the tumor showed the presence of ACTH-producing cells. The patient went into clinical and laboratorial remission after surgery. She re-started to grow after the disappearance of the Cushing's phenotype but she is still shorter than her healthy sister. The latter remains disease-free 4 years after her sister's diagnosis. This represents the third such case reported in the literature. Our findings suggest that acquired factors may be responsible for the genesis of Cushing's disease.

[A technology with multiple applications]. / Uma tecnologia com múltiplas aplicações.

Plant breeding has been a human practice for some thousands of years. However, this process of domestication has made plants more vulnerable to pests and diseases. Classic plant breeding has allowed the genetic manipulation of plants through crossings with a resulting increase in crop productivity. Recently, the recombinant DNA technology has increased the possibilities of integration of exogenous genes to the plant genome, resulting in the production of transgenic plants. Despite the great debate on this issue, such plants represent to date a promising avenue for plant breeding. There are many examples of gene transference strategies which have been successful in promoting resistance to herbicides, viruses, fungi, bacteria and insects, or in producing an increase in food quality. In addition to biotechnological applications, transgenic plants have made a significant contribution to the study of gene functioning, such as the analysis of genic expression regulation and the study of protein functions codified by distinct plant genes.

Interferon-α induced psoriatic arthritis and autoimmune hemolytic anemia during chronic hepatitis C treatment.

Chronic hepatitis C (CHC) can occur simultaneously with a myriad of rheumatic diseases or can induce autoimmunity. Inflammatory arthropathy is the main extra-hepatic manifestation of infection by virus C. In addition, the treatment for CHC with INF-α and ribavirin is also able to cause some immune-mediated events. The present case report describes an unusual case of psoriatic arthritis (PsA) and autoimmune hemolytic anemia (AIHA) during therapy for CHC.

Discriminatory ability of quantitative ultrasound measurements is similar to dual-energy X-ray absorptiometry in a Brazilian women population with osteoporotic fracture.

The discriminating ability and relevance of clinical risk factors, quantitative ultrasound (QUS) variables, X-ray-based bone mineral density (BMD) and hip axis length (HAL) measurements to evaluate the risk of osteoporotic fracture in elderly Brazilian women were examined in this study. QUS at the calcaneus (Achilles +, Lunar), HAL and BMD measurements (DPX-L, Lunar) at several anatomical sites were performed in 275 postmenopausal Caucasian women. Patients with suspected secondary osteoporosis were excluded. One hundred twenty-two (44.4%) women had had previous osteoporotic fracture. All of the subjects were over 50 years old (range 53-93) and answered a questionnaire that included details concerning aspects of lifestyle, diet, hormonal factors and drug use. Lateral thoracic and lumbar radiographs were taken and an independent radiologist reviewed the X-rays for the presence of vertebral fractures. After adjustments for age, the most relevant risk factors to discriminate patients with osteoporotic fracture from normal non-fracture controls were Stiffness index (OR 2.8 per standard deviation; 95% confidence interval 2.3, 8.7), familial history of hip fracture (OR 2.6 per standard deviation; 95% confidence interval 2.2, 5.4), femoral neck BMD (OR 2.3 per standard deviation; 95% confidence interval 1.9, 4.2), age (OR 2.1 per standard deviation; 95% confidence interval 1.6, 2.8) and weight (OR 1.9 per standard deviation; 95% confidence interval 1.5, 2.6). HAL measurements did not associate significantly with the risk of hip fracture in this population. The ability of QUS measurements discriminate between patients with fractures from those without was similar to, if not better, than X-ray-based BMD measurements. However, a combination of QUS and BMD measurements did not significantly improve fracture discrimination compared with either technique alone. Association of clinical risk factors with QUS or BMD measurements seems, on the other hand, to increase the sensibility to identify patients at risk of osteoporotic fractures.

Prevalence of low trauma fractures in long-term kidney transplant patients with preserved renal function

We evaluated the prevalence of low bone mineral density (BMD) and osteoporotic fractures in kidney transplantation (KT) patients and determined risk factors associated with osteoporotic fractures. The study was conducted on 191 patients (94 men and 97 women) with first KT for 3 years or more presenting stable and preserved renal function (serum creatinine levels lower than 2.5 mg/dl). KT patients were on immunosuppressive therapy and the cumulative doses of these drugs were also evaluated. BMD was determined by dual-energy X-ray absorptiometry at multiple sites (spine, femur and total body). Quantitative ultrasound of the calcaneus (broadband ultrasound attenuation, speed of sound, and stiffness index, SI) was also performed. Twenty-four percent (46) of all patients had either vertebral (29/46) or appendicular (17/46) fractures. We found osteoporosis and osteopenia in 8.5-13.4 and 30.9-35.1 percent of KT patients, respectively. Women had more fractures than men. In women, prevalent fractures were associated with diabetes mellitus [OR = 11.5, 95 percent CI (2.4-55.7)], time since menopause [OR = 3.7, 95 percent CI (1.2-11.9)], femoral neck BMD [OR = 1.99, 95 percent CI (1.4-2.8)], cumulative dose of steroids [OR = 1.1, 95 percent CI (1.02-1.12)] and low SI [OR = 1.1, 95 percent CI (1.0-1.2)]. In men, fractures were associated with lower lumbar spine BMD [OR = 1.75, 95 percent CI (1.1-2.7)], lower SI [OR = 1.1, 95 percent CI (1.03-1.13)], duration of dialysis [OR = 1.3, 95 percent CI (1.13-2.7)], and lower body mass index [OR = 1.24, 95 percent CI (1.1-1.4). Our results demonstrate high prevalence of low BMD and osteoporotic fractures in patients receiving a successful kidney transplant and indicate the need for specific intervention to prevent osteoporosis in this population.