Endocrine Abstracts

JOINT3974

Introduction: Hypophosphatasia (HPP) is a rare metabolic bone disorder characterized by low levels of tissue-nonspecific alkaline phosphatase (TNSALP) due to mutations in the ALPL gene. Deficiency of this alkaline phosphatase (ALP) isoform has been associated mainly with bone and dental disorders. However, although muscle alterations are frequent, muscle functionality is a scarcely evaluated aspect in patients with PPH. The aim of this study was to demonstrate the functional and structural impairment of bone and skeletal muscle in HPP.

Materials and Methods: Observational study of adult subjects with a genetic diagnosis of HPP and healthy controls, matched for sex, age and body mass index (BMI). The following clinical variables were collected: muscle strength measured with Jamar dynamometer; quadriceps rectus femoris muscle mass (Y-axis, X-axis, area and circumference) measured with ultrasound (Sonosite S-Nerve®); fat-free mass (FFM) and bone mineral density (BMD) in total hip, femoral neck (FN) and lumbar spine determined by dual-energy X-ray absorptiometry. Statistical analysis was performed with IBM SPSS v.26.

Results: Thirty-four PPH cases (48 years±18; 55% women), matched for age, sex and BMI with a control group, were analyzed. Median and interquartile range (IQR) of bone (BMD), muscle (dynamometry, Y-axis, X-axis, area and circumference), adiposity and biochemical (ALP) parameters were determined in both groups. Age-adjusted dynamometry values were significantly lower in the HPP group (28.6Kg vs 34.3; P = 0.039). Similarly, significant differences were observed in BMD of FN (0.8g/cm² vs 0.9; P = 0.034) with the HPP group presenting lower values. No significant differences were observed in muscle mass. Analyzing muscle strength values in relation to ALP quartiles, a positive correlation was observed between both variables, highlighting significant differences between the first and fourth quartiles (P = 0.003). Multiple linear regression results showed an independent association between ALP levels and muscle strength (B=0.103 (95%CI 0.032-0.175), P = 0.005).

Conclusions: Impaired muscle strength was observed independently of muscle mass in patients with HPP, especially in those with more decreased ALP levels, suggesting that ALP level seems to be an important determinant of muscle strength. This could be related to bone status, particularly at the femoral level.