Skeletal disorders associated with skin pigmentation: a role of melatonin? M. E. Abdel-Wanis, N. Kawahara Department of Orthopaedic Surgery, Faculty of Medicine, Kanazawa University, Kanazawa, Japan Summary Although frequently encountered, no available consensus about the association between skeletal abnormalities and skin pigmentation. Several syndromes are characterized by the presence of skin pigmentation in association with skeletal disorders like neurofibroamtosis 1, McCune–Albright Syndrome, Jaffe–Campanacci Syndrome and Jaffe–Lichtenstein Syndrome. Even in the absence of these syndromes, skeletal abnormalities were detected in all radiologically examined patients having patterned skin pigmentation. Although skin pigmentation is controlled by several factors, melatonin is the most reliable factor to have relation to development of skeletal abnormalities. Recent research works support that melatonin might play a role in bone development and several hypotheses link melatonin with some bone diseases associated with skin pigmentation. It seems that melatonin deficiency is a probable operating co-factor in a lot of clinical situations characterized by skin pigmentation and skeletal disorders. This would explain some of the un-explained observations related to these syndromes and research works along these lines might lead to the development of efficient treatment for these diseases. ª 2003 Published by Elsevier Ltd. INTRODUCTION Although frequently encountered, no available consen- sus about the association between skeletal disorders and skin pigmentation. Skeletal abnormalities were detected in 100% of radiologically examined patients having patterned skin pigmentation (1). Additionally, several syndromes are characterized by the presence of skin pigmentation in association with skeletal disorders like neurofibroamtosis 1, McCune–Albright Syndrome, Jaffe– Campanacci Syndrome and Jaffe–Lichtenstein Syndrome (2–8). Skin pigmentation could not be attributed to the primary genetic aberrations recognized in these syn- dromes because pigmentation in these syndromes could be identical in a lot of instances (3). Moreover, although neurofibromatosis 1 is attributed to loss of function of neurofibromin (the protein encoded by the neurofibro- matosis 1 gene) (7,8), analysis of skin from neurofibro- matosis 1 patients showed normal neurofibromin expression in nine of ten hyperpigmented caf e-au-lai macules and in adjacent unaffected skin (9). Interest- ingly, several bony abnormalities are repeatedly found in syndromes associated with skin pigmentation (2–8); that could obviate the possibility that these bony ab- normalities are pure result of the genetic aberrations. For example, intraosseous fibrous defects are the main skeletal abnormalities in Jaffe–Campanacci Syndrome as well as frequent findings in neurofibromatosis 1 (2,4). Also, fibrous dysplasia tissue is sometimes found at the sites of bone pseudarthrosis frequently associate neuro- fibromatosis 1 (10). Moreover, although fibrous dyspla- sia is a component of Jaffe–Lichtenstein Syndrome, to date – to our knowledge – no mutations characteristic of fibrous dysplasia have been reported in this syndrome in 640 Received 8 February 2002 Accepted 8 May 2002 Correspondence to: Dr. Mohamed E. Abdel-Wanis, Department of Orthopaedic Surgery, Faculty of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. Phone: +81-76-265- 2374; Fax: +81-76-234-4261; E-mail: wanis307@yahoo.com Medical Hypotheses (2003) 61(5–6), 640–642 ª 2003 Published by Elsevier Ltd. doi:10.1016/S0306-9877(03)00265-2