The major factors that determine whether a person develops osteoporosis are the maximum (peak) bone density that is achieved and the amount that is subsequently lost. Bone quality and architecture are also important. Peak bone mass in men and women is probably achieved soon after their skeletal growth ceases. Peak bone mass is largely determined by genetic factors. The variance in bone mineral density between dizygotic twins is much greater than in monozygotic twins, and the daughters of women who have had a hip fracture have lower than average bone mineral density. Excessive exercise may lead to hypothalamic-induced hypoestrogenism which, in turn, results in reduced bone mineral density. Smoking is associated with a reduced peak bone mass, earlier menopause, and thinness, all of which are risk factors for osteoporotic fracture. The active form of vitamin D, 1,25-dihydroxyvitamin D has important physiologic activities, including upregulating intestinal calcium and phosphate absorption.