Serum osteocalcin level is associated with the mortality in Chinese patients with Fibrodysplasia ossificans progressiva aged ≤18 years at diagnosis

Background Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear. Methods We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality. Results 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G>A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, non-survivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors ( P <0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the non-survivors from survivors in FOP patients aged 18 years and younger at diagnosis. Conclusions Our findings showed that the mortality rate of FOP was 13.8% in China. Serum OC level was negatively correlated with the mortality in Chinese FOP patients ≤18 years at diagnosis. 【 Key words 】Fibrodysplasia ossificans progressive (FOP); mortality; risk factors; osteocalcin

Serum osteocalcin may serve as a predictor for the mortality in FOP patients aged ≤18 years at diagnosis

Background Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear. Methods We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality. Results 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G>A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, non-survivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors ( P <0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the non-survivors from survivors in FOP patients aged 18 years and younger at diagnosis. Conclusions Our findings showed that the mortality rate of FOP was 13.8% in China. Serum osteocalcin may serve as a clinical predictor for the mortality in FOP patients aged ≤18 years at diagnosis in China. 【 Key words 】Fibrodysplasia ossificans progressive (FOP); mortality; risk factors; osteocalcin

Serum osteocalcin may serve as a predictor for the mortality in FOP patients aged ≤18 years at diagnosis

Background Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear. Methods We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality. Results 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G>A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, non-survivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors ( P <0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the non-survivors from survivors in FOP patients aged 18 years and younger at diagnosis. Conclusions Our findings showed that the mortality rate of FOP was 13.8% in China. Serum osteocalcin may serve as a clinical predictor for the mortality in FOP patients aged ≤18 years at diagnosis in China. 【 Key words 】Fibrodysplasia ossificans progressive (FOP); mortality; risk factors; osteocalcin

Serum osteocalcin may serve as a predictor for the mortality in FOP patients aged ≤18 years at diagnosis

Background Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear. Methods We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality. Results 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G>A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, non-survivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors ( P <0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the non-survivors from survivors in FOP patients aged 18 years and younger at diagnosis.Conclusions Our findings showed that the mortality rate of FOP was 13.8% in China. Serum osteocalcin may serve as a clinical predictor for the mortality in FOP patients aged ≤18 years at diagnosis in China. 【 Key words 】Fibrodysplasia ossificans progressive (FOP); mortality; risk factors; osteocalcin

Muscle, Connective Tissue, and Neonatal Disorders

The skeleton provides the framework and anchor points against which muscles, attached via tendons, can exert force. Three types of cells are involved in making bone: osteoblasts, osteoclasts, and cartilage. The human muscle system is made up of three types of muscle tissue: skeletal, cardiac, and smooth. The neonate period of life is the first 4 weeks after the birth of an infant. This chapter presents 11 genetic disorders that affect muscles, connective tissue, and newborns. These include achondroplasia, Charcot-Marie tooth syndrome, Duchenne Muscular Dystrophy, Ellis-Van Creveld syndrome, amyotrophic lateral sclerosis, Marfan syndrome, fibrodysplasia ossificans progressive, myotonic dystrophy, Angelman syndrome, Prader-Willi syndrome, fragile-X syndrome, and Waardenburg syndrome.

Fibrodysplasia Ossificans Progressiva: A Case Report

Fibrodysplasia ossificans progressiva is a genetic disorder of the connective tissue differentiation characterized by congenital malformation of the big toes and progressive heterotopic ossification in the extra skeletal tissues like tendons, ligaments, fascia and skeletal muscles leading to permanent disability. The prevalence is one in two million people. During childhood, it may be asymptomatic but in later life, progressive stiffness of major joints renders movement of the individual impossible. Currently, there is no effective treatment for this debilitating disease. Here, we present a case of 27 year old male with clinical and radiological features of fibrodysplasia ossificans progressiva.Keywords: Fibrodysplasia ossificans progressive; heterotopic ossification; myositis ossificans; myositis ossificans progressive.

Bone

This chapter discusses the anatomy and physiology of the bone, including mineralization, and outlines techniques in bone remodelling. It describes formation and resorption hormonal markers that are part of the bone remodelling cycle, such as procollagens and serums. It describes how diagnostic measures in these formation markers are increased for focal bone disorders like Paget’s disease, fibrous dysplasia, osteomalacia, bone metastases, myeloma, primary hyperparathyroidism, thyrotoxicosis, and acromegaly. The chapter also discusses osteoporosis, including causes, symptoms, and treatment options. Clinical suggestions for bone diagnoses and diseases are provided, based on dual-energy X-ray absorptiometry (commonly abbreviated as DXA), plain radiography, and bone biopsy. The chapter also defines osteogenesis imperfecta and describes its epidemiology and management. In addition, it outlines sclerosing bone disorders such as osteopetrosis, pycnodysostosis, and hyperostosis type Worth, as well as fibrodysplasia ossificans progressive.