RESUMO
The aim of this paper is to review the main aspects related to high bone density (HBD) as well as to discuss the physiologic mechanisms involved in bone health. There are still no well-defined criteria for identification of individuals with HBD and there are few studies on the topic. Most studies demonstrate that overweight, male gender, black ethnic background, physical activity, calcium and fluoride intake and use of medications such as statins and thiazide diuretics play a relevant and positive role on bone mineral density. Moreover, it is known that individuals with certain diseases such as obesity, diabetes, estrogen receptor-positive breast or endometrial cancer have greater bone density than healthy individuals, as well as athletes having higher bone density than non-athletes does not necessarily mean that they have healthy bones. A better understanding of risk and protective factors may help in the management of patients with bone frailty and have applicability in the treatment and in the prevention of osteoporosis, especially intervening on non-modifiable risk factors.
Assuntos
Densidade Óssea , Osso e Ossos/metabolismo , Hiperostose/etiologia , Animais , Atletas , Composição Corporal , Peso Corporal , Densidade Óssea/genética , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Remodelação Óssea , Cálcio/metabolismo , Dieta , Difosfonatos/farmacologia , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/fisiopatologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperostose/genética , Hiperostose/fisiopatologia , Metabolismo dos Lipídeos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/fisiologia , Masculino , Osteoblastos/metabolismo , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Vitamina D/farmacologia , Suporte de Carga , Proteínas Wnt/fisiologiaRESUMO
Sclerosteosis is a severe, rare, autosomal recessive bone condition that is characterized by a progressive craniotubular hyperostosis. The main features are a significant sclerosis of the long bones, ribs, pelvis, and skull, leading to facial distortion and entrapment of cranial nerves. Clinical features include a tall stature, nail dysplasia, cutaneous syndactyly of some fingers, and raised intracranial pressure. The sclerosteosis gene has been mapped to chromosome 17q12-21 and is currently known as the SOST gene encoding the sclerostin protein. Here, we report on one familial and one isolated case of Brazilian origin with the clinical and molecular diagnosis of sclerosteosis. The radiological and clinical features are described, and the diagnosis of sclerosteosis was confirmed in both cases by mutation analysis of the SOST gene showing a homozygous nonsense mutation (Trp124X) in the two patients. We reported this mutation previously in other sclerosteosis patients from a consanguineous Brazilian family. Interestingly, all three families were from the same state in Brazil, but they denied familial relationship. These patients confirm the clinical picture as found in other cases with a loss of function mutation in the SOST gene.
Assuntos
Proteínas Morfogenéticas Ósseas/genética , Códon sem Sentido , Marcadores Genéticos/genética , Hiperostose/genética , Osteosclerose/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Brasil , Criança , Feminino , Homozigoto , Humanos , Hiperostose/diagnóstico por imagem , Hiperostose/patologia , Masculino , Osteosclerose/diagnóstico por imagem , Osteosclerose/patologia , Radiografia , Adulto JovemRESUMO
Craniotubular hyperostosis are a group of high bone mass disorders related to mutations in the LRP5 and SOST genes, although other causative genes remain to be identified. Little is known about the bone turnover and the response to T3 or glucocorticoids in these patients. We describe a patient with craniotubular hyperostosis, including mutation analyses of the LRP5, SOST, DKK1 and KRM1 genes. We also studied bone turnover and bone mineral density (BMD), before and after a trial with T3 (75 microg/d for 28 weeks) and T3 and prednisone (T3 100 microg/d for 2 weeks, followed by 10 weeks on prednisone 10 mg/d, and a final 2 weeks period off of medicactions, completing 3 cycles in 42 weeks. Mutation analysis of the complete coding region and flanking highly conserved sequences of SOST, evaluation of the presence of the 52-kb deletion associated with Van Buchem disease in Dutch patients and mutation analysis of exons 2-4 of LRP5, and the coding regions of DKK1 and KRM1 did not reveal any disease-causing mutations. A baseline 5 to 7 fold increase in osteocalcin and in deoxypiridinoline was detected. After 4 weeks on 75 microg/d of T3, osteocalcin decreased 36%, but at week 28, it returned to basal. Deoxypiridinoline did not change. After the first cycle on T3 and prednisone, osteocalcin decreased 72%, and at the end of the third cycle it remained 44% below basal value. Deoxypiridinoline was stable and high during the three cycles; no changes in BMD were observed. As we failed to identify any disease-causing mutations in our patient with craniotubular hyperostosis, we suggest that another gene must be involved in the pathogenesis of his condition. This study provides additional data about the high bone turnover described in craniotubular hyperostosis, and also suggests an abnormal response to T3 excess in this condition.