Bone Abstracts

Alkaline phosphatase activity is critical for the mineralization of the bone matrix. Indeed, inactivating mutations of the ALPL gene, encoding the isoenzyme expressed in bone and liver, may result in the severe abnormalities of bone and other connective tissues that characterize hypophosphatasia. Nevertheless, the clinical spectrum of hypophosphatasia is rather broad and variable between a within families. Thus, along severe infantile forms, there are adult forms with mild manifestations that may be incidentally discovered by the presence of low alkaline phosphatase activity in serum. Some of those patients may be heterozygote carriers of mutations of the ALPL gene. They may be asymptomatic or have only minor ailments. Yet, it is unclear whether those patients have a normal BMD or not.

In order to clarify this issue, we evaluated spine and hip BMD in 20 individuals with persistently low serum alkaline phosphatase activity (six men and 14 women; mean age 57 years, range 20–77). The results were compared with a group of 80 age- and sex-matched controls.

After sequencing the exons and exon-intron boundaries of the ALPL gene, a mutated allele was found in 10 patients. Patients and controls had the same height and weight. They also had similar BMD at the spine (1.028±0.182 g/cm² in patients; and 0.960±0.190 g/cm² in controls, P=0.15) and the femoral neck (0.816±0.151 vs 0.785±0.129 g/cm²). In line with these results, there were no significant differences in the age-adjusted BMD between patients with and without ALPL mutations. The mean trabecular bone score (TBS) was 1.41±0.09; in all cases it was higher than 1.20, the lower limit of the normal range.

In conclusion, this study suggests that patients with heterozygous mutations of the ALPL gene have normal BMD, despite the fact that they have persistently low levels of serum alkaline phosphatase.