New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65

Stress fractures

ABSTRACT Stress fractures (SF) represent 10%-20% of all injuries in sport medicine. An SF occurs when abnormal and repetitive loading is applied on normal bone: The body cannot adapt quickly enough, leading to microdamage and fracture. The etiology is multifactorial with numerous risk factors involved. Diagnosis of SF can be achieved by identifying intrinsic and extrinsic factors, obtaining a good history, performing a physical exam, and ordering laboratory and imaging studies (magnetic resonance imaging is the current gold standard). Relative energy deficiency in sport (RED-S) is a known risk factor. In addition, for women, it is very important know the menstrual status to identify long periods of amenorrhea in the past and the present. Early detection is important to improve the chance of symptom resolution with conservative treatment. Common presentation involves complaints of localized pain, with or without swelling, and tenderness on palpation of bony structures that begins earlier in training and progressively worsens with activity over a 2- to 3-week period. Appropriate classification of SF based on type, location, grading, and low or high risk is critical in guiding treatment strategies and influencing the time to return to sport. Stress injuries at low-risk sites are typically managed conservatively. Studies have suggested that calcium and vitamin D supplementation might be helpful. Moreover, other treatment regimens are not well established. Understanding better the pathophysiology of SFs and the potential utility of current and future bone-active therapeutics may well yield approaches that could treat SFs more effectively.

Association between fractures and traditional risk factors for osteoporosis and low bone mineral density in patients with obesity

ABSTRACT Objective: To evaluate the reasons for request of bone mineral density (BMD) evaluation and correlate the BMD results with previous fractures, risk factors for osteoporosis, and clinical characteristics in patients with obesity. Subjects and methods: Cross-sectional, retrospective, single-site study including adult patients with body mass index (BMI) ≥ 30 kg/m2 and BMD evaluation between January 2015 and May 2016 selected from a BMD database. Data on demographic characteristics, lifestyle habits, comorbidities, medications, risk factors, previous fractures, and indications for BMD evaluation were collected from the participants' medical records. Results: The study included 619 patients (89.9% women, mean BMI 34.79 ± 4.05 kg/m2). In all, 382 (61.7%), 166 (26.8%), and 71 (11.5%) patients had class 1, 2, and 3 obesity, respectively. The most frequent (29.9%) reason for BMD evaluation was for osteoporosis monitoring. In all, 69.4% of the patients had low BMD. Multivariate analysis showed that age, calcium supplementation, and previous osteoporosis or osteopenia were associated with low BMD, while age, vitamin D supplementation, use of proton pump inhibitors (PPIs), and low BMD were associated with previous fractures (p < 0.05 for all). Conclusions: Among patients with obesity identified from a tertiary hospital database, those with low bone mass and risk factors traditionally associated with fractures had an increased history of fractures. Patients with greater BMI had better bone mass and fewer fractures. These findings indicate that the association between reduced weight, risk factors for osteoporosis, and fractures remained despite the presence of obesity in our population.

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso)

ABSTRACT Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC)

ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL

Body composition and nutritional and metabolic parameters in postmenopausal women sufficient, insufficient and deficient in vitamin D

ABSTRACT Objective We investigated changes in body composition and nutritional and metabolic parameters in a group of postmenopausal women who were classified as sufficient, insufficient and deficient in vitamin D. Subjects and methods A total of 106 postmenopausal women were included in this cross-sectional study and classified according to their serum levels of 25-OH-vitamin D as sufficient (≥ 30 ng/mL; group S), insufficient (20.1 and 29.9 ng/mL; group I) or deficient (≤ 20 ng/mL; group D) in vitamin D. Body composition was measured by dual-energy X-ray absorptiometry (DXA); dietary recall questionnaires were completed; and blood samples were analysed to compare the metabolic and nutritional status of the study groups. Results Eleven (10.4%) of the women were classified in group S, 50 (47.2%) in group I and 45 (42.4%) in group D, with a mean serum level for 25-OH-D of 21.1 ± 7.0 ng/mL in all participants. Body composition did not differ among the groups. Serum levels of 25-OH-D were negatively correlated with serum levels of triglycerides, total cholesterol and LDL cholesterol. Conclusions Vitamin D insufficiency and deficiency were highly prevalent in our group of postmenopausal women, showing an association with an unfavourable lipid profile.

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Sarcopenia in COPD: relationship with COPD severity and prognosis / Sarcopenia na DPOC: relação com a gravidade e o prognóstico da DPOC

Objective: To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.Methods: A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.Results: We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2. Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.Conclusions: In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.

Objetivo: Avaliar a prevalência de sarcopenia em pacientes com DPOC e determinar se sarcopenia está correlacionada com a gravidade e o prognóstico de DPOC.Métodos: Estudo retrospectivo em pacientes com DPOC atendidos no ambulatório de pneumologia de nossa instituição. Os pacientes realizaram absorciometria de dupla energia por raios X. O diagnóstico de sarcopenia foi baseado no índice de massa muscular esquelética, definido como massa magra apendicular/altura2 somente para indivíduos com baixo peso, sendo ajustado pela massa gorda para aqueles com peso normal/sobrepeso. A gravidade da doença (estádio da DPOC) foi avaliada com os critérios da Global Initiative for Chronic Obstructive Lung Disease (GOLD). O grau de obstrução e o prognóstico foram determinados pelo índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE).Resultados: Foram incluídos 91 pacientes (50 mulheres), com média de idade de 67,4 ± 8,7 anos e média de IMC de 25,8 ± 6,1 kg/m2. Sarcopenia foi diagnosticada em 36 (39,6%) dos pacientes, sem diferenças relacionadas a sexo, idade ou status tabágico. Não houve associação de sarcopenia com estádios GOLD ou VEF1 (utilizado como indicador do grau de obstrução). O IMC, a porcentagem de gordura corporal e a massa magra total foram menores nos pacientes com sarcopenia do que naqueles sem a doença (p < 0,001). A prevalência de sarcopenia foi maior nos pacientes com BODE nos quartis 3 ou 4 que naqueles com BODE nos quartis 1 ou 2 (p = 0,009). A análise multivariada mostrou que os quartis do BODE estavam significativamente associados à sarcopenia, independentemente de idade, gênero, status tabágico e estádio GOLD.Conclusões: Em pacientes com DPOC, sarcopenia parece estar associada a alterações desfavoráveis na composição corporal e pior prognóstico.

Síndrome da mäo rígida em pacientes diabéticos / The stiff hand syndrome in diabetic patients

A síndrome da Mäo Rígida acomete pacientes diabéticos fazendo rigidez, fraqueza e diminuiçäo da capacidade para realizar movimentos finos. Foram estudados 105 pacientes portadores de diabetes, visando avaliar a ocorrência da SMR nesta populaçäo, tendo encontrado 56 por cento de portadores da mesma. Näo se encontrou correlaçäo entre a ocorrência da síndrome com controle, tempo e tipo de DM, idade e sexo do paciente. Destaca-se o pouco reconhecimento desta entidade, bem como sua importância social