Osteomalacia as a Result of Vitamin D Deficiency Arti Bhan, MBBS a , Ajay D. Rao, MD b , D. Sudhaker Rao, MBBS c, * Among the metabolic bone diseases with known pathogenic mechanisms, osteopo- rosis is the most common and osteomalacia is the least common disorder. Neverthe- less, osteomalacia occurs with regular frequency such that it may escape recognition especially in its early stages because of the often indefinite symptoms such as vague bone pain and muscle weakness. In reality, however, osteomalacia is an end-stage bone disease of severe vitamin D or phosphate depletion of any cause with character- istic biochemical, radiological, and bone histologic features. The descriptive term osteomalacia originally referred to a generalized softening of bone leading to crippling deformities, and is almost always caused by vitamin D deficiency, and rarely by phos- phate and calcium depletion. 1 The cardinal histologic bone feature of osteomalacia is an excessive accumulation of unmineralized or poorly mineralized bone matrix. 1 In contrast, rickets (see the article by Thandrayen and Pettifor elsewhere in this issue for further exploration of this topic) is a disease of impaired mineralization of cartilage resulting in defective enchondral bone formation. By definition, therefore, rickets occurs only in children and adolescents before epiphyseal fusion, whereas osteoma- lacia occurs in children and in adults. Although this is an important clinical distinction, the pathogenesis of rickets and osteomalacia is similar. HISTORICAL PERSPECTIVE AND SCOPE OF THE PROBLEM The first description of osteomalacia was by Gustav Pommer, a German pathologist, in the late nineteenth century who discussed the histologic differences between osteomalacia, osteoporosis, and osteitis fibrosa. 1 One of the earliest reports of osteomalacia studied by tetracycline-based bone histomorphometry of the ribs was reported from Henry Ford Hospital in 1966. 2 Based on current concepts of bone a Division of Endocrinology, Diabetes and Bone & Mineral Disorders, Henry Ford Hospital, De- troit, MI 48202, USA b Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA c Bone & Mineral Research Laboratory, Henry Ford Hospital, E&R Building 7th Floor, 2799 West Grand Boulevard, Detroit, MI 48202, USA * Corresponding author. E-mail address: srao1@hfhs.org KEYWORDS  Osteomalacia  Vitamin D deficiency  Secondary hyperparathyroidism  Treatment Endocrinol Metab Clin N Am 39 (2010) 321–331 doi:10.1016/j.ecl.2010.02.001 endo.theclinics.com 0889-8529/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved.