Premature graying of hair is associated with several endocrine disorders, vitiligo, and the aging process. Although the pathophysiology of melanin depletion in hair follicles is unknown, genetic factors regulate the expression of this trait. As acquisition of bone mass is also genetically determined, we performed an exploratory case control study of the association between premature graying of hair and osteopenia (lumbar bone density t score, below -1.0). Subjects were recruited from a single metabolic bone clinic. Premature graying of hair in 36 men and women with osteopenia (cases) was compared to that in 27 men and women without osteopenia (controls). Subjects with premature graying but no other identifiable risk factor were 4.4 times as likely to have osteopenia as subjects without premature graying (P = 0.02). Subjects with osteopenia and premature graying in their teens and twenties had a stronger family history of osteoporosis than those who had osteopenia and graying later in their thirties (P = 0.06), but bone density and other characteristics were not different. The association between premature graying and low bone mass could be related to genes that control peak bone mass or factors that regulate bone turnover. Premature graying of hair may be an important risk marker for osteopenia.