ORIGINAL ARTICLE Longitudinal monitoring of bone accretion measured by quantitative multi-site ultrasound (QUS) of bones in patients with delayed puberty (a pilot study) Zvi Zadik Æ Tali Sinai Æ Ella Borondukov Æ Amnon Zung Irit Yaniv Æ Ram Reifen Received: 2 June 2004 / Accepted: 7 October 2004 / Published online: 23 December 2004 Ó International Osteoporosis Foundation and National Osteoporosis Foundation 2004 Abstract Objective: to compare the effect of anabolic agents on bone accretion in boys with constitutional delay of puberty (CGDP). Rationale: it has been sug- gested that an appropriate timing of puberty is necessary for normal bone mineral density (BMD) acquisition. Proper bone development during childhood is the key factor in achieving higher peak bone mass during middle age, which may not be achievable in CGDP children, and thereby osteoporosis may appear at an earlier age then expected. Patients and methods: 45 boys with CGDP aged 14–16 years were monitored longitudinally, every 3 months over 12 months with Sunlight Omni- sense, a quantitative ultrasound device (Tel Aviv, Israel). The apparatus is a multi-site bone sonometer that ob- tains axial Speed of Sound (SOS). Based on a reference database obtained on n=1,085 (490 boys) 0–18 years, a normative curve was determined. Fifteen (14–16 years old) of the CGDP patients were treated with I.M. test- ovirone depot 100 mg monthly for 6 months, 15 (14– 16 years old) were treated with oxandrolone 5 mg/m 2 daily for 6 months, and 15 (14–16 years old) were in an observation group. Results: whereas the quantitative ultrasound (QUS) Z-score had shown some increase over time in CGDP-treated patients, an increase was found in tibia Z-score from )0.5()0.64, )0.36) to )0.4()0.54, )0.26) and from )0.52()0.67, )0.38) to )0.31()0.44, )0.11) in the testosterone and oxandro- lone-treated groups, respectively, [median (25%, 75%)]. An increase in radius Z-score from )0.52()0.65, )0.25) to )0.4()0.54, )0.15) and from )0.51()0.61, )0.21) to )0.37()0.47, )0.07) in the testosterone- and oxandro- lone-treated groups respectively [median (25%,75%)]. Z-score SOS decreased in the observation group )0.5()0.66, )0.3) to )0.69()0.85, )0.54) and )0.5()0.59, )0.41) to )0.81()0.95, )0.55) in tibia (P = 0.032) and radius (P = 0.029), respectively. Despite the fact that QUS remained in the normative range in all patients, a clear deterioration was demonstrated in un- treated CGDP patients. Conclusion: longitudinal fol- low-up of patients with CGDP may detect an early pattern of deterioration of bone mass. Keywords Androgens Æ Bone ultrasound Æ Delayed puberty Æ Osteoporosis Æ Oxandrolone Introduction Decreased bone density has been reported in healthy adult men with a history of CGDP at different sites: radial [1], spinal [1, 2], and femoral [2] bones. These studies utilized dual-energy X-ray absorptiometry (DEXA). When puberty is inordinately delayed, bone mineral accretion may not be optimal; peak bone mass achievement may be impaired [1, 2] and thus increase the risk for osteoporotic fractures later in adult life [2]. The stigma of appearing less mature than one’s peers in CDGP boys can lead to social and academic prob- lems. Signs of puberty may reassure these teens, improve their self-esteem and enable them to function better among their peers [3]. Therefore, management of CDGP aims to optimize growth while maintaining body pro- portions without impairing growth potential, as well as to minimize the distress associated with being short and immature. Thus far, anabolic steroids have been widely used for the improvement of growth and the rate of pubertal development in children with CDGP [4]. Ox- androlone, an oral growth-promoting synthetic agent Osteoporos Int (2005) 16: 1036–1041 DOI 10.1007/s00198-004-1795-y Z. Zadik (&) Æ E. Borondukov Æ A. Zung The Pediatric Endocrine Unit, Kaplan Medical Center, Hadassah Medical School, 76100 Rehovot, Israel E-mail: zvizadik@012.net.il Fax: +972-8-9411942 Z. Zadik Æ T. Sinai Æ R. Reifen The School of Nutritional Sciences, The Hebrew University of Jerusalem, Israel I. Yaniv Sunlight Medical, Tuval 5, Tel-aviv, Israel