Hypercalcemia Associated with Pregnancy and Lactation.

Hypercalcemia during pregnancy is a risk for adverse maternal and fetal consequences. Although primary hyperparathyroidism is by far the most common etiology of hypercalcemia in pregnancy, an array of other etiologies of hypercalcemia associated with pregnancy and lactation have been described. Parathyroidectomy continues to be the preferred treatment for primary hyperparathyroidism. Medical management options are limited.

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Interactions between PTH and adiposity: appetizing possibilities.

Although parathyroid hormone (PTH) is best known for its role as a regulator of skeletal remodelling and calcium homeostasis, more recent evidence supports a role for it in energy metabolism and other non-classical targets. In this report, we summarize evidence for an effect of PTH on adipocytes. This review is based upon all peer-reviewed papers, published in the English language with PubMed as the primary search engine. Recent preclinical studies have documented an effect of PTH to stimulate lipolysis in both adipocytes and liver cells and to cause browning of adipocytes. PTH also reduces bone marrow adiposity and hepatic steatosis. Although clinical studies are limited, disease models of PTH excess and PTH deficiency lend support to these preclinical findings. This review supports the concept of PTH as a polyfunctional hormone that influences energy metabolism as well as bone metabolism.

Parathyroid hormone controls skeletal and circulating calcium levels. Its secretion by the four parathyroid glands is regulated primarily by the concentration of the ionized calcium level. The other major target organ for parathyroid hormone is the kidney where it conserves filtered calcium by effects on the renal tubules. While bone and the kidney are indisputably the main target organs for PTH, recent studies are pointing to systems and organs that can be shown also to respond to PTH. One of these systems that PTH appears to target is fat cells, an important storehouse for energy. This review summarizes what is known about PTH's effects to stimulate the production of energy from fat cells when present in excess or to reduce the production of energy when deficient.

New insights into the vitamin D/PTH axis in endocrine-driven metabolic bone diseases.

BACKGROUND: Endocrine regulation of bone metabolisms is the focus of the "Skeletal Endocrinology" series of meetings. AIMS: To report on the outcome of the discussion on the role of vitamin D/PTH axis in endocrine osteopathies held during the 10th Skeletal Endocrinology Meeting which took place in Stresa (Italy) in March 2023. OUTCOMES: Vitamin D/PTH axis has relevant influence on several outcomes in the general population and in patients affected by endocrinopathies such as hypoparathyroidism and secreting pituitary adenomas. CONCLUSIONS: Assessing the status of the vitamin D/PTH axis and using vitamin D and PTH as therapeutic agents is mandatory in several endocrine-related bone metabolic conditions.

Massive 4-Gland Parathyroid Hyperplasia Initially Detected as a Parathyroid Adenoma.

Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery. Abnormalities in the parathyroid glands can be identified with various imaging modalities including ultrasound (US), sestamibi scan (MIBI), 4-dimensional computed tomography (4D-CT), and positron emission tomography/computed tomography (PET/CT). While it is not uncommon for parathyroid pathology to be undetected on imaging, this is more typical of low-volume hyperplasia and smaller-sized adenomas. We present the case of a 65-year-old man with PHPT who initially had a solitary parathyroid mass detected by US, but who was ultimately discovered to have massive PH with hyperplastic glands not visualized on US or MIBI. This atypical presentation may help guide providers in decisions on ordering and interpreting various imaging modalities for patients with PHPT. In this case, 4D-CT was the only modality in which large hyperplastic glands were identified, suggesting superior sensitivity. This case also highlights the importance of intraoperative parathyroid hormone testing to aid in diagnostic prediction.

Male osteoporosis

ABSTRACT Osteoporosis, a disease classically attributed to postmenopausal women, is underappreciated, underdiagnosed, and undertreated in men. However, it is not uncommon for osteoporotic fractures to occur in men. About 40% of fractures occur in men with an incidence that has increased over the years. After a first fracture, the risk of a subsequent episode, as well as the risk of death, is higher in the male than in the female population. Despite these facts, only 10% of men with osteoporosis receive adequate treatment. Up to half of the cases of male osteoporosis have a secondary cause, the most common being hypogonadism, excessive alcohol consumption, and chronic use of glucocorticoids. The International Society for Clinical Densitometry (ISCD) recommends using the female database for the diagnosis of osteoporosis by DXA (T-score ≤ −2.5 in men over 50 years old). In addition, osteoporosis can also be diagnosed independently of the BMD if a fragility fracture is present, or if there is a high risk of fractures by FRAX. Treatment is similar to postmenopausal osteoporosis, because the data regarding changes in bone density track closely to those in women. Data concerning fracture risk reduction are not as certain because the clinical trials have included fewer subjects for shorter period of time. In men with symptomatic hypogonadism, testosterone replacement, if indicated, can improve BMD.

Long-term consequences of osteoporosis therapy with denosumab

ABSTRACT Denosumab (DMAb) is a human monoclonal antibody used as an antiresorptive drug in the treatment of osteoporosis. Approval at a dosage of 60 mg every 6 months was based on the results of the randomized, placebo-controlled trial (FREEDOM). The design of this 3-year study included an extension for up to 10 years. Those who were randomized to DMAb continued on drug, while those who were randomized to placebo transitioned to DMAb. The 10-year experience with DMAb provides data on efficacy of drug in terms of reduced fractures and continued increases in bone mineral density (BMD). The 10-year experience with denosumab also provides information about rare complications associated with the use of DMAb, such as osteonecrosis of the jaw (ONJ), and atypical femoral fractures (AFF). This experience provided new insights into the reversibility of effects upon discontinuation without follow-on therapy with another agent. This review focuses upon prolonged treatment with DMAb, with regard to beneficial effects on fracture reduction and safety. Additionally, its use in patients with impaired renal function, compare its results with those of bisphosphonates (BPs), the occurrence/frequency of complications, in addition to the use of different tools, from imaging techniques to histological findings, to evaluate its effects on bone tissue.

FGF23 levels as a marker of physical performance and falls in community-dwelling very old individuals

ABSTRACT Objective: The fibroblast growth factor 23 (FGF23) has been related to biological aging, but data in elderly individuals are scant. We determined the profile of serum FGF23 levels in a population of very-old individuals and studied their correlations with parameters of bone metabolism and health markers, as functional performance. Materials and methods: This cross-sectional study was performed on 182 community dwellers aged ≥ 80 years. Serum levels of FGF23, PTH, calcium, albumin, phosphorus, creatinine, bone markers, and bone mineral density data were analyzed. Physical performance was evaluated with the stationary march (Step), Flamingo, and functional reach tests, along with questionnaires to assess falls and fractures in the previous year, energy expenditure (MET), and the Charlson index (CI). Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ). Results: Most participants (75%) had FGF23 levels between 30-120 RU/mL (range: 6.0-3,170.0 RU/mL). FGF23 levels correlated with estimated glomerular filtration rate (eGFR; r = -0.335; p = 0.001) and PTH (r = 0.318; p < 0.0001). Individuals with FGF23 in the highest tertile had more falls in the previous year (p = 0.032), worse performance in the Flamingo (p = 0.009) and Step (p < 0.001) tests, worse CI (p = 0.009) and a trend toward sedentary lifestyle (p = 0.056). On multiple regression, FGF23 tertiles remained significant, independently of eGFR, for falls in the previous year, performance in the Flamingo and stationary march tests, lean mass index, and IPAQ classification. Conclusion: In a population of very elderly individuals, FGF23 levels were inversely associated with neuromuscular and functional performances. Higher concentrations were related to more falls, lower muscle strength and aerobic capacity, and poorer balance, regardless of renal function, suggesting a potentially deleterious role of high FGF23 concentrations in musculoskeletal health.

Incidence of vertebral fractures in calcium and vitamin D-supplemented postmenopausal Brazilian women with osteopenia or osteoporosis: data from Arzoxifene Generations Trial

ABSTRACT Objective Vertebral fracture is the most common osteoporotic fracture, affecting quality of life and increasing mortality. Epidemiological data on incidence of vertebral fracture are scarce in Brazil and throughout Latin America. Our aim was to determine vertebral fracture incidence and risk factors in a female Brazilian population. Subjects and methods Postmenopausal women with low bone mass were studied from the Brazilian placebo group of Arzoxifene Generations Trial (n = 974), followed for up to 5 years. The primary endpoint was new vertebral fractures, detected by X-Ray. Experimental design defined two strata: A. Osteoporosis or previous vertebral fracture with osteopenia; B. Osteopenia without previous fracture. Previous fracture, T-score, ionized calcium, alkaline phosphatase, creatinine and glucose were analyzed at baseline. Crude and adjusted incidence rates of vertebral fractures were estimated and Poisson regression model was used. Results Incidence rate was 7.7 (95% CI of 5.4 to 10.9) per 1,000 person-years (PY), increasing as a function of age. Women with new vertebral fractures had higher prevalence of previous nonvertebral fracture after menopause, were older and had lower lumbar spine (LS) T-score. Fracture risk increased by 46% for each unit reduction in LS T-score. Variables correlated with new vertebral fracture were age (p = 0.034), LS T-score, stratum A (p = 0.001 for both) and previous nonvertebral fracture after menopause (p = 0.019). In the final model, LS T-score was the strongest predictor. Conclusions Incidence rate of vertebral fracture of 7.7 per 1,000 PY. Age and previous fractures were associated with new vertebral fracture, but LS T-score was the most important predictor.

Bone disease in primary hyperparathyroidism / Doença óssea no hiperparatiroidismo primário

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.

A doença óssea no hiperparatiroidismo primário grave é representada pela osteíte fibrosa cística (OFC). Dor óssea, deformidades esqueléticas e fraturas patológicas são achados comuns na OFC. A densidade mineral óssea está, usualmente, extremamente diminuída na OFC, mas é reversível após a cura cirúrgica. Os sinais e sintomas da doença óssea grave incluem dor óssea, fraturas patológicas e fraqueza muscular proximal com hiper-reflexia. O comprometimento ósseo é tipicamente caracterizado pela aparência em “sal-e-pimenta” nos ossos do crânio, erosões ósseas e reabsorção das falanges, tumores marrons e cistos. Na radiografia, observam-se desmineralização difusa e fraturas patológicas especialmente nos ossos longos das extremidades. No hiperparatiroidismo primário (HPTP) sintomático grave, as concentrações séricas de cálcio e PTH estão usualmente bem elevadas e o comprometimento renal se caracteriza pela presença de urolitíase e nefrocalcinose. Uma nova tecnologia, recentemente aprovada para uso clínico nos Estados Unidos e na Europa, torna-se provável se difundir rapidamente, pois utiliza as imagens geradas pela densitometria DXA. O escore trabecular ósseo (TBS), obtido por meio da análise do nível da textura cinza das imagens dos corpos vertebrais, fornece informações indiretas sobre a microarquitetura trabecular. Novos métodos, como a tomografia de alta resolução quantitativa periférica computadorizada (HRpqCT), têm proporcionado conhecimentos adicionais sobre os achados da microarquitetura esquelética no HPTP.

Bone markers and osteoporosis therapy / Marcadores de turnover ósseo e tratamento da osteoporose

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.

Diversos fatores estão envolvidos na determinação da qualidade óssea, incluindo a densidade óssea, a remodelação óssea, a extensão da conectividade do osso trabecular, porosidade cortical e geometria. Metabolicamente ativo e, em um processo contínuo de remodelação, cerca de 20% do tecido ósseo é renovado anualmente. Por sua vez, marcadores de turnover ósseo (BTM) são frequentemente utilizados em estudos clínicos e fornecem informações válidas sobre a eficácia do tratamento da osteoporose, o que reflete o metabolismo ósseo e sua resposta ao tratamento, embora eles não sejam úteis somente para estimar a perda óssea. Nesta revisão, o comportamento dos BTM em ensaios clínicos diferentes e com diferentes drogas osteoporóticas será abordado.

Trabecular bone score: perspectives of an imaging technology coming of age / Escore de osso trabecular: perspectivas de um método de imagem em aprimoramento

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.

TBS (do inglês, “trabecular bone score”) é um novo método que estima a microarquitetura óssea a partir de uma imagem de densitometria óssea (DXA) da coluna lombar. Apesar de o TBS não ser uma medida física direta da microarquitetura trabecular, ele correlaciona-se com o volume ósseo, densidade da conectividade trabecular, número de trabéculas e separação trabecular medidos por microtomografia computadorizada (µCT), e com medidas mecânicas da resistência óssea vertebral em estudos ex vivo. Estudos em humanos confirmaram que o TBS associa-se a microarquitetura trabecular e resistência óssea medidas por tomografia computadorizada quantitativa periférica de alta resolução (HRpQCT). Estudos transversais e prospectivos, envolvendo um grande número de indivíduos, mostraram que o TBS é associado com fratura vertebral, de colo de fêmur e com outros tipos de fraturas osteoporóticas em mulheres na pós-menopausa. Dados em homens, apesar de escassos, mostram resultados semelhantes. Além disso, o TBS foi associado a fraturas por fragilidade em indivíduos com diversas causas secundárias de osteoporose e, dados preliminares, sugerem que o uso do TBS pode melhorar a previsão de fratura quando incorporado ao sistema de avaliação de risco de fratura (FRAX). Este artigo faz uma revisão de avanços recentes que têm ajudado a estabelecer esse novo método de imagem.

Accelerated fracture healing with teriparatide / Consolidação de fratura acelerada com teriparatida

Satisfactory healing of the osteoporotic fracture is critically important to functional recovery, morbidity, and quality of life. Some therapies for osteoporosis may affect the processes associated with bone repair. For example, bisphosphonates in experimental models are associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. For the osteoanabolic agent teriparatide, case reports and a randomized trial have produced mixed results, but they are consistent with a positive impact of teriparatide on fracture healing. Some of the agents currently being developed for osteoporosis, notably sclerostin and DKK1 antibodies have shown a beneficial effect on fracture healing. At this point, therefore, there is no evidence that osteoporosis therapies are detrimental to fracture healing with some promising experimental evidence for positive effects on healing, notably for those agents whose actions are primarily anabolic.

A consolidação adequada da fratura osteoporótica é essencial para recuperação funcional, morbidade e qualidade de vida. Alguns tratamentos para osteoporose podem afetar os processos associados ao reparo ósseo. Por exemplo, os bisfosfonatos, em modelos experimentais, estão associados com aumento do tamanho do calo e a mineralização, reduzindo o remodelamento do calo e melhorando a força mecânica. Tratamento com bisfosfonato, local ou sistêmico, pode melhorar a fixação de implantes. Não foi observado impacto negativo na consolidação da fratura, mesmo após uma cirurgia maior ou quando administrado imediatamente após a fratura. Relatos e um estudo randomizado com o osteoanabólico teriparatida produziram resultados mistos, mas que são consistentes com o impacto positivo da teriparatida na consolidação da fratura. Algumas das drogas que estão sendo desenvolvidas no momento para osteoporose, como anticorpos para esclerotina e DKK1, têm mostrado efeito benéfico na consolidação da fratura. No estágio atual, portanto, não há evidência de que terapias para osteoporose impeçam a consolidação da fratura, mas existem algumas evidências experimentais promissoras de efeito positivo na consolidação, especialmente daqueles agentes cuja ação é primariamente anabólica.

Normocalcemic primary hyperparathyroidism / Hiperparatiroidismo normocalcêmico primário

Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease.

O hiperparatiroidismo primário (HPTP) é uma doença comum caracterizada por uma regulação inadequada da secreção do paratormônio em uma ou mais glândulas paratiroides. Historicamente a doença pode ser dividida em duas eras. Quando o HPTP foi descoberto há 80 anos, era sempre sintomático com nefrolitíase, doença óssea e acentuada hipercalcemia. Com o advento das rotinas laboratoriais por autoanalisadores bioquímicos há 40 anos, o fenótipo clínico mudou para uma doença sintomaticamente leve na ausência daqueles achados clássicos. Está se entrando numa terceira era em que os pacientes são diagnosticados com calcemia normal na presença de níveis circulantes elevados do paratormônio. Neste artigo, descreve-se essa nova entidade, hiperparatiroidismo primário normocalcêmico, uma forma frusta da doença.

Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement / Hipoparatiroidismo: aspectos clínicos, microestrutura esquelética e reposição do paratormônio

OBJECTIVE: Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. SUBJECTS AND METHODS: Standard histomorphometric and µCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. RESULTS: Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. CONCLUSION: Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D.

OBJETIVO: O hipoparatiroidismo é uma doença em que há diminuição dos níveis circulantes do paratormônio, em geral, causada por destruição autoimune ou exerese cirúrgica. O objetivo deste estudo foi descrever as anormalidades microestrutrurais esqueléticas, como também o potencial terapêutico do uso do PTH(1-84). SUJEITOS E MÉTODOS: Histomorfometria padrão e análise de micro-CT foram realizadas em biópsias de crista ilíaca de indivíduos com hipoparatiroidismo. Os participantes foram tratados com PTH(1-84) por dois anos. RESULTADOS: A densidade óssea aumentou e os achados esqueléticos refletiram o estado de baixa remodelação óssea com maior BV/TV, Tb Wi e CT Wi, como também supressão de MS e BFR/BS quando comparado com o grupo controle. Com o uso de PTH(1-84), a remodelação óssea aumentou e a densidade óssea aumentou na coluna lombar. As necessidades de cálcio e vitamina D diminuíram e a calciúria não mudou. CONCLUSÃO: A microestrutura esquelética anormal no hipoparatiroidismo reflete a ausência do PTH. A terapia de reposição com PTH tem o potencial de reverter essas anormalidades, como também reduzir as necessidades de cálcio e vitamina D.

Glucocorticoid-Induced osteoporosis: clinical and therapeutic aspects: [review]

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30_50 percent of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. Glucocorticoids have direct and indirect effects on the skeleton. They impair the replication, differentiation, and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO.

A osteoporose induzida por glicocorticóides (OIG) é a forma mais comum de osteoporose secundária. Fraturas, que são freqüentemente assintomáticas, podem ocorrer em até 30_50 por cento dos pacientes recebendo terapia glicocorticóide crônica. Fraturas vertebrais ocorrem logo após exposição aos glicocorticóides, ocasião em que a densidade mineral óssea (DMO) diminui rapidamente. As fraturas tendem a ocorrer mais com níveis elevados de DMO do que em mulheres com osteoporose da pós-menopausa. Os glicocorticóides têm efeitos diretos e indiretos sobre o esqueleto: eles impedem a replicação, a diferenciação e a função dos osteoblastos e induzem apoptose dos osteoblastos maduros e osteócitos. Esses efeitos levam à supressão da formação óssea, uma manifestação central da patogênese da OIG. Os glicocorticóides também favorecem a osteoclastogênese e, como conseqüência, aumentam a reabsorção óssea. Os bisfosfonatos são a mais efetiva das várias terapias que têm sido avaliadas para o manuseio da OIG. Estratégias terapêuticas com anabolizantes estão sendo investigadas. O teriparatídeo parece também ser eficaz no tratamento de pacientes com OIG.

Bone density and bone turnover markers in patients with epilepsy on chronic antiepileptic drug therapy

In this comparative, cross-sectional study, we evaluated 55 patients with epilepsy on chronic use of antiepileptic drugs (AED); [(38 females and 17 males, 35 ± 6 years (25 to 47)] and compared to 24 healthy subjects (17 females/7 males). Laboratorial evaluation of bone and mineral metabolism including measurements of bone specific alkaline phosphatase (BALP) and carboxyterminal telopeptide of type I collagen (CTX-I) were performed. Bone mineral density (BMD) was measured by DXA. BALP and CTX-I levels did not differ significantly between the groups. CTX-I levels were significantly higher in patients who were exposed to phenobarbital (P< 0.01) than those who were not. Patients presented BMD of both sites significantly lower than the controls (0.975 ± 0.13 vs. 1.058 ± 0.1 g/cm²; p= 0.03; 0.930 ± 0.1 vs. 0.988 ± 0.12 g/cm²; p= 0.02, respectively). Total hip BMD (0.890 ± 0.10 vs. 0.970 ± 0.08 g/cm²; p< 0.003) and femoral neck (0.830 ± 0.09 vs. 0.890 ± 0.09 g/cm²; p< 0.03) were significantly lower in patients who had been exposed to phenobarbital, in comparison to the non-phenobarbital users. In conclusion, patients on AED demonstrate reduced BMD. Among the AED, phenobarbital seems to be the main mediator of low BMD and increases in CTX-I.

Neste estudo comparativo, transversal, 55 pacientes com epilepsia [38 mulheres e 17 homens; 35 ± 6 anos (25 a 47anos)] foram comparados com 24 indivíduos normais (17 mulheres / 7 homens). Foi realizada uma avaliação laboratorial do metabolismo ósseo e mineral incluindo a dosagem de fosfatase alcalina específica óssea (BALP) e telopeptídeo carboxiterminal do colágeno tipo I (CTX-I). Densidade mineral óssea (DMO) da coluna lombar e do fêmur foi medida por DXA. BALP e CTX-I não foram diferentes entre os grupos. CTX-I foi significativamente mais elevado nos pacientes expostos ao fenobarbital do que os que não usaram essa medicação (p< 0,01). DMO de ambos os sítios foi menor no grupo de pacientes (0,975 ± 0,13 vs. 1,058 ± 0,1 g/cm²; p= 0,03; 0,930 ± 0,1 vs. 0,988 ± 0,12 g/cm²; p= 0,02, respectivamente). DMO do fêmur total (0,890 ± 0,10 vs. 0,970 ± 0,08 g/cm²; p< 0,003) e colo do fêmur (0,830 ± 0,09 vs. 0,890 ± 0,09 g/cm²; p< 0,03) foi significativamente menor nos pacientes que usaram fenobarbital. Em conclusão, pacientes portadores de epilepsia em uso crônico de drogas antiepilépticas (DAE) demonstraram uma redução da DMO. Entre as DAE, o fenobarbital parece ser o principal mediador da diminuição da DMO e do aumento do CTX-I.