Alkaline Phosphatase as a Potential Biomarker of Muscle Function: A Pilot Study in Patients with Hypophosphatasia

Alkaline phosphatase (ALP) deficiency has been linked to reduced physical performance, as seen in hypophosphatasia (HPP). However, its potential role in muscle function has not been fully explored. This was a cross-sectional study in 34 HPP adults and 34 matched healthy controls. Muscle strength was assessed using handgrip strength (HGS), considering values below the 10th percentile of the Spanish population as low strength. Muscle mass was evaluated using dual-energy X-ray absorptiometry and morphometric ultrasound. Bone mineral density (BMD) was measured at the lumbar spine, femoral neck, and total hip. The prevalence of low muscle strength was significantly higher in the HPP group compared to controls (30% vs. 6%; p = 0.009), with decreased HGS in the HPP group (p = 0.039). Positive associations were observed between ALP and femoral neck BMD, leg circumference, and fat-free mass and an inverse association with tricipital skinfold. Subjects with serum ALP activity below the sex-adjusted median had a significantly higher risk of low muscle strength independently of HPP diagnosis. ALP remained independently associated with HGS (p = 0.005), and a predictive model using ALP values showed strong capability to predict low-muscle-strength risk. Based on these results, we conclude circulating ALP levels are independently associated with muscle strength and may represent a useful biomarker for the early detection of muscle dysfunction. Future longitudinal or interventional studies are needed to assess whether ALP plays a causal role in muscle strength.