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

Abstract

Background: Fibrodysplasia ossificans progressiva (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, nonsurvivors 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 nonsurvivors 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.

Bone phenotypes in rheumatology – there is more to bone than just bone

“… [ 28 , 29 ] Osteocalcin Osteoporosis: not diagnostic Osteopetrosis: reduced in ADOII patients FOP: inconclusive Osteoporosis: Modulated in response to pharmacological interventions such as bisphosphonates, anti-sclerostin and anti-RANKL. FOP: Age dependent association with mortality [ 28 – 30 ] (B)ALP Osteoporosis: not diagnostic Osteopetrosis: no difference in ADOII patients Osteoporosis: Modulated in response to pharmacological interventions such as bisphosphonates, anti-sclerostin and anti-RANKL. [ 28 , 29 , 31 ] TRACP5b Osteoporosis: Elevated compared to healthy controls Osteopetrosis: Increased in ADOII Increased in in vivo models Osteoporosis: associated with markers of bone remodeling and BMD.…”

“…Only few biomarker studies have been undertaken in FOP patients, likely due to the detrimental effects of even light invasive techniques such as blood sampling (Table 1 ). The only report on bone markers in serum, to our knowledge, include bone formation markers osteocalcin and ALP but focus has been on aspects such as mortality rather than structural alterations, making it difficult to interpret pathology derived alterations in levels [ 30 ].…”