Clinical, biochemical and genetic findings in adult patients with chronic hypophosphatasemia

Purpose The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP). Methods Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5’-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies. Results Pathogenic ALPL variants (p ALPL ) occurred in 23% and benign variants in 36% of patients (b ALPL ), while nine patients harbored wild-type alleles (wt ALPL ). Fragility fractures and dental anomalies were more frequent in patients harboring p ALPL and b ALPL than in wt ALPL patients. Of note, wt ALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were similar in the three groups. Mean urine PEA levels were significantly higher in patients harboring p ALPL than those detected in patients harboring b ALPL and wt ALPL ; by contrast, serum PLP levels were similar in the three groups. A 6-points score, considering clinical and biochemical features, was predictive of p ALPL detection [ P = 0.060, OR 1.92 (95% CI 0.972, 3.794)], and more significantly of p ALPL or b ALPL [ P = 0.025, OR 14.33 (95% CI 1.401, 14.605)]. Conclusion In osteopenic/osteoporotic patients, single clinical or biochemical factors did not distinguish hypophosphatasemic patients harboring p ALPL or b ALPL from those harboring wt ALPL . Occurrence of multiple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.