Theoretical analysis of contributions of disuse, basic multicellular unit activation threshold, and osteoblastic formation threshold to changes in bone mineral density at menopause

Although bone loss at menopause is known to be associated with disuse and estrogen deficit, their contributions and mechanisms are not completely clear. This article presents a computer simulation aimed at clarifying the contributions of various factors that may be responsible for osteoporosis in women. We utilized a mechanical-biological coupled model at the level of basic multicellular units (BMUs) to quantify disuse, changes in BMU activation threshold, and changes in osteoblastic formation threshold on a representative cross section of 100 mm2 of cancellous bone in the lumbar spine of a postmenopausal woman. The separate and combined contributions were determined by a total of 17 parametrical analyses through comparison to clinical data presented in the literature. An increase in osteoblastic formation threshold alone cannot explain the bone loss patterns seen clinically. Bone mineral density predictions were much closer to the clinical data for the simulation of a maintained increase in BMU activation threshold during menopause or some time after menopause. Maintained disuse alone would result in high rates of bone loss long after menopause. A combination of disuse and an increase in osteoblastic formation threshold, or of an increase in BMU activation threshold and an increase in osteoblastic formation threshold, or of disuse and an increase in BMU activation threshold, or a combination of these three is capable of describing the bone loss found at menopause. It was found that disuse and an increase in the BMU activation threshold may be the major contributors to bone loss at menopause. Understanding the contributions of disuse and the changes in the BMU activation threshold and in the osteoblastic formation threshold that occur at menopause may help to gain more insight into the mechanism of osteoporosis and identify improved osteoporosis treatment and prevention.