INTRODUCTIONrnA loss-of-function mutation in the liver/bone/kidney alkaline phosphatase (ALPL) gene results in the life-threatening disease hypophosphatasia (HPP) during early developmental periods; HPP is characterized by hypomineralization of the skeleton and teeth.1-2 Adult patients with HPP showed early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, and fractures. Our previous study found age-related bone mass loss and marrow fat gain in heterozygous Alpl+/- mice.3 Bone marrow mesenchymal stem cells (BMSCs) are multipotent cells capable of differentiating into various cell lineages, including osteoblasts and adipocytes. As age increases, BMSCs are more inclined to undergo differentiation into adipocytes rather than osteoblasts, resulting in an increased number of adipocytes and a decreased number of osteoblasts, which leads to osteoporosis.4 Our previous study also showed that ALPL goved the osteo-adipogenic balance in BMSCs and prevented cell senescence.