Griz L, Fontan D, Mesquita P
… +7 more, Lazaretti-Castro M, Borba VZ, Borges JL, Fontenele T, Maia J, Bandeira F, Brazilian Society of Endocrinology and Metabolism
Arq Bras Endocrinol Metabol
· 2014 Aug · PMID 25211441
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OBJECTIVE: To conduct a literature review on the diagnosis and management of Paget's disease of bone. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AM...OBJECTIVE: To conduct a literature review on the diagnosis and management of Paget's disease of bone. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on Paget's disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.
Normocalcemic primary hyperparathyroidism (NPHPT) is a condition characterized by elevation of the parathyroid hormone (PTH) in the presence of normal serum calcium and the absence of secondary causes. The case described...Normocalcemic primary hyperparathyroidism (NPHPT) is a condition characterized by elevation of the parathyroid hormone (PTH) in the presence of normal serum calcium and the absence of secondary causes. The case described illustrates the long-term follow-up of a postmenopausal woman with NPHPT patient who progressed with multiple adenomas. This case reports a 77-year-old female who has chronic generalized pain and osteoporosis. Her initial serum PTH was 105 pg/mL, with total serum calcium of 9.6 mg/dL, albumin 4.79 g/dL, phosphorus 2.8 mg/dL, and 25OHD after supplementation was 34.6 ng/mL. The bone densitometry (BMD) results were as follows: lumbar spine: T-score -3.0, femoral neck: T-score -2.6 and distal radius: -4.2. Other causes of secondary hyperparathyroidism were ruled out and cervical ultrasound and Tc-99-Sestamibi scan were negative. She used oral alendronate and three infusions of zoledronic acid for treatment of osteoporosis. In the 10th year of follow-up, after successive negative cervical imaging, ultrasound showed a nodule suggestive of an enlarged right inferior parathyroid gland. PTH levels in fluid which was obtained during fine-needle aspiration (FNA) were over 5,000 pg/mL and a Sestamibi scan was negative. The patient underwent parathyroidectomy, and a histological examination confirmed parathyroid adenoma. Post-operatively serum PTH remained elevated in the presence of normal serum calcium levels. A follow-up cervical ultrasound showed a new solid nodule suggestive of an enlarged right superior parathyroid gland. PTH levels in the aspiration fluid were remarkably high. A second parathyroidectomy was performed, with the excision of a histologically confirmed parathyroid adenoma. In conclusion, this is an unusual presentation of NPHPT and highlights the long-term complications.
Objectives To evaluate the serum 25-hydroxyvitamin D [25(OH)D] concentration in Brazilian osteoporotic patients and the modifiable factors of vitamin D status in this population. Subjects and methods In a cross-sectional...Objectives To evaluate the serum 25-hydroxyvitamin D [25(OH)D] concentration in Brazilian osteoporotic patients and the modifiable factors of vitamin D status in this population. Subjects and methods In a cross-sectional study, 363 community-dwelling patients who sought specialized medical care were evaluated between autumn and spring in São Paulo, Brazil. Serum levels of 25(OH)D and parathormone (PTH), biochemical and anthropometric measurements, and bone density scans were obtained. The group was assessed using two questionnaires: one questionnaire covered lifestyle and dietary habits, skin phototype, sun exposure, medical conditions, and levels of vitamin D supplementation (cholecalciferol); the other questionnaire assessed health-related quality-of-life. Logistic regression and a decision tree were used to assess the association between the variables and the adequacy of vitamin D status. Results The mean age of the overall sample was 67.9 ± 8.6 years, and the mean 25(OH)D concentration was 24.8 ng/mL. The prevalence of inadequate vitamin D status was high (73.3%), although 81.5% of the subjects were receiving cholecalciferol (mean dose of 8,169 IU/week). 25(OH)D was positively correlated with femoral neck bone mineral density and negatively correlated with PTH. In the multivariate analysis, the dose of cholecalciferol, engagement in physical activity and the month of the year (September) were associated with improvement in vitamin D status. Conclusions In this osteoporotic population, vitamin D supplementation of 7,000 IU/week is not enough to reach the desired 25(OH)D concentration (≥ 30 ng/mL). Engagement in physical activity and the month of the year are modifiable factors of the vitamin D status in this population.
Secondary hyperparathyroidism (HPT) has a high prevalence in renal patients. Secondary HPT results from disturbances in mineral homeostasis, particularly calcium, which stimulates the parathyroid glands, increasing the s...Secondary hyperparathyroidism (HPT) has a high prevalence in renal patients. Secondary HPT results from disturbances in mineral homeostasis, particularly calcium, which stimulates the parathyroid glands, increasing the secretion of parathyroid hormone (PTH). Prolonged stimulation can lead to autonomy in parathyroid function. Initial treatment is clinical, but parathyroidectomy (PTx) may be required. PTx can be subtotal or total followed or not followed by parathyroid tissue autograft. We compared the indications and results of these strategies as shown in the literature through a systematic literature review on surgical treatment of secondary HPT presented in MedLine and LILACS from January 2008 to March 2014. The search terms were: hyperparathyroidism; secondary hyperparathyroidism; parathyroidectomy and parathyroid glands, restricted to research only in humans, articles available in electronic media, published in Portuguese, Spanish, English or French. We selected 49 articles. Subtotal and total PTx followed by parathyroid tissue autograft were the most used techniques, without consensus on the most effective surgical procedure, although there was a preference for the latter. The choice depends on surgeon's experience. There was consensus on the need to identify all parathyroid glands and cryopreservation of parathyroid tissue whenever possible to graft if hypoparathyroidism arise. Imaging studies may be useful, especially in recurrences. Alternative treatments of secondary HPT, both interventional and conservative, require further study.
Arq Bras Endocrinol Metabol
· 2014 Jul · PMID 25166047
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Full text
Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density i...Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT.
Hypoparathyroidism is a rare disorder that may be acquired or inherited. Postsurgical hypoparathyroidism is responsible for the majority of acquired hypoparathyroidism. Bone disease occurs in hypoparathyroidism due to ma...Hypoparathyroidism is a rare disorder that may be acquired or inherited. Postsurgical hypoparathyroidism is responsible for the majority of acquired hypoparathyroidism. Bone disease occurs in hypoparathyroidism due to markedly reduced bone remodeling due to the absence or low levels of parathyroid hormone. Chronically reduced bone turnover in patients with hypoparathyroidism typically leads to higher bone mass than in age- and sex-matched controls. Whether this increased bone density reduces fracture risk is less certain, because while increased bone mineralization may be associated with increased brittleness of bone, this does not appear to be the case in hypoparathyroidism. Treatment of hypoparathyroidism with recombinant parathyroid hormone may reduce bone mineral density but simultaneously strengthen the mechanical properties of bone.
Vitamin D deficiency has been linked to bone fragility in children and adults, and to an increased risk of chronic diseases. The main sources of vitamin D are the diet and cutaneous synthesis, the latter being the most i...Vitamin D deficiency has been linked to bone fragility in children and adults, and to an increased risk of chronic diseases. The main sources of vitamin D are the diet and cutaneous synthesis, the latter being the most important one, since foods are relatively poor in vitamin D. The main factors influencing this endogenous production are the seasons, the time of day, latitude and skin phototype. Due to the contribution of sun exposure in maintaining vitamin D levels, it would be expected that this deficiency would be more prevalent in countries at a high latitude; it has been shown, however, that hypovitaminosis D is commonly found in tropical regions such as Brazil. In high latitude regions in which extreme skin phototypes have been compared, the prevalence of vitamin D deficiency is more common in people with originally darker skin who have a natural barrier to the already lower UV irradiation penetrating the skin. In Brazil, particularly in the areas where sun rays are more abundant, the difference in sunlight exposure between subjects showed no significant variation in serum 25-hydroxyvitamin D (25OHD).
Aging is associated with decreases in bone quality and in glomerular filtration. Consequently, osteoporosis and chronic kidney disease (CKD) are common comorbid conditions in the elderly, and often coexist. Biochemical a...Aging is associated with decreases in bone quality and in glomerular filtration. Consequently, osteoporosis and chronic kidney disease (CKD) are common comorbid conditions in the elderly, and often coexist. Biochemical abnormalities in the homeostasis of calcium and phosphorus begin early in CKD, leading to an increase in fracture risk and cardiovascular complications since early stages of the disease. The ability of DXA (dual energy X-ray absorptiometry) to diagnose osteoporosis and to predict fractures in this population remains unclear. The management of the disease is also controversial: calcium and vitamin D, although recommended, must be prescribed with caution, considering vascular calcification risk and the development of adynamic bone disease. Furthermore, safety and effectiveness of osteoporosis drugs are not established in patients with CKD. Thus, risks and benefits of antiosteoporosis treatment must be considered individually.
The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-ma...The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a "drug holiday," which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks.
Physical exercise is an important stimulus for osteoporosis prevention and treatment. However, it is not clear yet which modality would be better to stimulate bone metabolism and enhance physical function of postmenopaus...Physical exercise is an important stimulus for osteoporosis prevention and treatment. However, it is not clear yet which modality would be better to stimulate bone metabolism and enhance physical function of postmenopausal women. This review paper aims to summarize and update present knowledge on the effects of different kinds of aquatic and ground physical exercises on bone metabolism and physical function of postmenopausal women. Moderate to intense exercises, performed in a high speed during short intervals of time, in water or on the ground, can be part of a program to prevent and treat postmenopausal osteoporosis. Mechanical vibration has proven to be beneficial for bone microarchitecture, improving bone density and bone strength, as well as increasing physical function. Although impact exercises are recognized as beneficial for the stimulation of bone tissue, other variables such as muscle strength, type of muscle contraction, duration and intensity of exercises are also determinants to induce changes in bone metabolism of postmenopausal women. Not only osteoanabolic exercises should be recommended; activities aimed to develop muscle strength and body balance and improve the proprioception should be encouraged to prevent falls and fractures.
Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process...Several factors are involved in determining bone quality including bone density, bone turnover, the extent of trabecular bone connectivity, cortical porosity and geometry. Metabolically active and in a continuous process of remodeling, approximately 20% of bone tissue is renewed annually. Bone turn over markers (BTM) are frequently used in clinical trials and to provide valid information about the effectiveness of osteoporosis treatment, reflecting the state of bone metabolism and its response to treatment, although they are not useful alone to estimate bone loss. In this review the behavior of BTM from different clinical trials or different osteoporotic drugs will be addressed.
The trabecular bone score (TBS) is a new method to describe skeletal microarchitecture from the dual energy X-ray absorptiometry (DXA) image of the lumbar spine. While TBS is not a direct physical measurement of trabecul...The trabecular bone score (TBS) is a new method to describe skeletal microarchitecture from the dual energy X-ray absorptiometry (DXA) image of the lumbar spine. While TBS is not a direct physical measurement of trabecular microarchitecture, it correlates with micro-computed tomography (µCT) measures of bone volume fraction, connectivity density, trabecular number, and trabecular separation, and with vertebral mechanical behavior in ex vivo studies. In human subjects, TBS has been shown to be associated with trabecular microarchitecture and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT). Cross-sectional and prospective studies, involving a large number of subjects, have both shown that TBS is associated with vertebral, femoral neck, and other types of osteoporotic fractures in postmenopausal women. Data in men, while much less extensive, show similar findings. TBS is also associated with fragility fractures in subjects with secondary causes of osteoporosis, and preliminary data suggest that TBS might improve fracture prediction when incorporated in the fracture risk assessment system known as FRAX. In this article, we review recent advances that have helped to establish this new imaging technology.
Organ transplantation is the gold standard therapy for several end-stage diseases. Bone loss is a common complication that occurs in transplant recipients. Osteoporosis and fragility fractures are serious complication, m...Organ transplantation is the gold standard therapy for several end-stage diseases. Bone loss is a common complication that occurs in transplant recipients. Osteoporosis and fragility fractures are serious complication, mainly in the first year post transplantation. Many factors contribute to the pathogenesis of bone disease following organ transplantation. This review address the mechanisms of bone loss including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac and bone marrow transplantation. Prevention and management of bone loss in the transplant recipient should be included in their post transplant follow-up in order to prevent fractures.
With the advent of high active antiretroviral therapy there was a significant improvement on HIV subjects survival. Thus, bone changes related to HIV became an important aspect of these individuals. HIV affects bone remo...With the advent of high active antiretroviral therapy there was a significant improvement on HIV subjects survival. Thus, bone changes related to HIV became an important aspect of these individuals. HIV affects bone remodeling causing bone fragility. In addition, antiretroviral therapy may also negatively affect bone metabolism. Several studies describe an increased incidence of fractures in these patients when compared with controls without the disease. The European Society of AIDS (EACS), and other societies, have included guidance on management of osteoporosis in HIV-infected patients emphasizing the identification of patients with low bone mass. Supplementation of calcium and vitamin D and the use of alendronate in these individuals should be recommended on a case base.
Until recently obesity was believed to be protective against fractures. However, a report from a Fracture Liaison Clinic in the UK (2010) reported a surprisingly high proportion of obese postmenopausal women attending th...Until recently obesity was believed to be protective against fractures. However, a report from a Fracture Liaison Clinic in the UK (2010) reported a surprisingly high proportion of obese postmenopausal women attending the clinic with fractures, and in the GLOW study (2011), a similar prevalence and incidence of fractures in obese and non-obese postmenopausal women was observed. Subsequently, other studies have demonstrated the importance of obesity in the epidemiology of fractures. Obese women are at increased risk of fracture in ankle, leg, humerus, and vertebral column and at lower risk of wrist, hip and pelvis fracture when compared to non-obese women. In men, it has been reported that multiple rib fractures are associated with obesity. Furthermore, falls appear to play an important role in the pathogenesis of fractures in obese subjects. Regarding hip fracture and major fractures, the FRAX algorithm has proven to be a useful predictor in obese individuals. Obese people are less likely to receive bone protective treatment; they have a longer hospital stay and a lower quality of life both before and after fracture. Moreover, the efficacy of antiresorptive therapies is not well established in obese people. The latter is a field for future research.
Sarcopenia, the loss of muscle mass and function with age, is highly relevant to clinical practice as it has been associated with a wide range of ageing outcomes including disability and shorter survival times. As such i...Sarcopenia, the loss of muscle mass and function with age, is highly relevant to clinical practice as it has been associated with a wide range of ageing outcomes including disability and shorter survival times. As such it is now a major focus for research and drug discovery. There has been recent progress in the development of consensus definitions for the diagnosis of sarcopenia, taking the form of measurements of muscle mass and strength or physical performance. These definitions form potential inclusion criteria for use in trials, although the optimum choice of outcome measures is less clear. Prevalence estimates using these new definitions vary, although they suggest that sarcopenia is a common (approximately 13% from one study) clinical problem in older people. A range of lifestyle factors have been investigated in regard to the development of this condition, and progressive resistance training is the most well-established intervention so far. There is also marked research interest in the role of diet, although so far the value of supplementation is less clear. Other potential treatments for sarcopenia include the angiotensin-converting enzyme inhibitors, with some evidence that they can improve physical performance in older people. Future research directions include an increased understanding of the molecular and cellular mechanisms of sarcopenia and the use of a life course approach to explore the possibility of earlier intervention and prevention.
Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to ident...Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.
Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream an...Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome.
Osteoporotic fractures impose severe physical, psychosocial, and financial burden both to the patient and the society. Studies on the prevalence of osteoporosis and fragility fractures in Brazil show a wide variation, du...Osteoporotic fractures impose severe physical, psychosocial, and financial burden both to the patient and the society. Studies on the prevalence of osteoporosis and fragility fractures in Brazil show a wide variation, due to differences in sample size, the population studied, and methodologies. Few studies have been conducted in Brazil about the cost-effectiveness analyses of different intervention options aimed at the diagnosis and treatment of osteoporosis. Investigation and treatment strategies based on cost-effectiveness and scientific evidence are essential in the preparation of public health policies with the ultimate goal of reducing the incidence of fractures and, consequently, the direct and indirect costs associated with them. This article reviews the Brazilian burden of osteoporosis in terms of the prevalence and fractures attributable to the disease, the costs related to the investigation and management, as well as the impact of osteoporosis on the population as a whole and on affected individuals.
OBJECTIVE: The objective is to present an update on the diagnosis and treatment of hypovitaminosis D, based on the most recent scientific evidence. MATERIALS AND METHODS: The Department of Bone and Mineral Metabolism of...OBJECTIVE: The objective is to present an update on the diagnosis and treatment of hypovitaminosis D, based on the most recent scientific evidence. MATERIALS AND METHODS: The Department of Bone and Mineral Metabolism of the Brazilian Society of Endocrinology and Metabology (SBEM) was invited to generate a document following the rules of the Brazilian Medical Association (AMB) Guidelines Program. Data search was performed using PubMed, Lilacs and SciELO and the evidence was classified in recommendation levels, according to the scientific strength and study type. CONCLUSION: A scientific update regarding hypovitaminosis D was presented to serve as the basis for the diagnosis and treatment of this condition in Brazil.