Congenital isolated GH deficiency causes joint problems, reduces bone size but does not cause reduced bone density

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 624-646-Growth: Clinical Trials & Observational Studies
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-643
Carlos E Epitácio-Pereira*1, Gabriella M. F. Silva2, Roberto Salvatori3, João A. M. Santana4, Francisco A Pereira5, Carla R .P. Oliveira6, Anita H O. Souza7, Elenilde G. Santos7, Viviane C. Campos8, Rossana M.C Pereira9, Eugênia H. O. Valença7, Francisco J A De paula10, Taisa V. Ribeiro4 and Manuel H Aguiar-Oliveira11
1FEDERAL UNIVERSITY OF SERGIPE, Aracaju, Brazil, 2Federal University Sergipe, Aracaju-SE, Brazil, 3Johns Hopkins Univ Sch of Med, Baltimore, MD, 4Federal University of Sergipe, Aracaju, Brazil, 5Federal University of Sergipe, Aracjau, Brazil, 6Univ Federal de Sergipe, Aracaju Sergipe, Brazil, 7Federal Univ Sergipe Univ Hosp, Aracaju-SE, Brazil, 8Univ Fed de Sergipe, Aracaju, Brazil, 9Universidad Federal de Sergipe, Aracaju, Brazil, 10School of Medicine of Ribeirão Preto of University of S.Paulo, Ribeirão Preto, Brazil, 11Federal Univ Sergipe Univ Hosp, Aracaju SE, Brazil
Background: The GH/IGF-I axis is important for bone growth and development, but its effects on the acquisition of bone mineral density (BMD) and on joint function are not completely understood.  Adult onset GH deficient (GHD) individuals have often reduced BMD. However, there is only a report that studied bone status in congenital lifetime isolated GHD (IGHD). This found a low areal BMD but normal volumetric BMO (vBMO) in 4 young men (23 to 30 yrs) with an inactivating GHRH-R mutation (1). Similarly, in 11 adult GH resistant individuals, vBMO was reported to be normal (2), but early osteoarthritis (OA) and some orthopedic problems (limitation of elbow extension and genum valgum) were observed.  We have previously shown that adult IGHD individuals with severe short stature due to the c.57+1G>A GHRHR mutation have reduced bone stiffness (3), but BMD, joint  function and structure in this cohort are unknown. The purposes of this work were to study BMD, joint function and OA severity in IGHD  adults of both genders.

Methods: Areal BMD (by DXA) was measured in 25 IGHD (13 males, 38.2±12.2 yrs, 129±10.7 cm) and 22 controls (CO) (9 males, 38.9±10.4 yrs, 163±9.8 cm). vBMD was calculated with the formula: BMDL1-L4/√Area L1-L4. Joint function was assessed by goniometry of elbow, hips and knees. X rays were used to measure the anatomic axis of knee and the severity of OA, defined by an adaptation of the Osteoarthritis Research Society International classification that accounts for joint space narrowing or osteophytes scores in the knees and hip. Student’s test was used to compare groups.

Results:  Height and weight standard deviation scores were lower in IGHD than CO (-6.47±1.52 vs. -0.98±0.89, p<0.0001 and -5.26±3.05 vs. 0.4±1.03, p<0.0001 respectively). Areal BMD (g/cm2) was lower in IGHD than CO at L1-L4 (0.94± 0.13 vs. 1.20±0.11, p = 0.0001) and total femur (0.91±0.09 vs. 1.05±0.14, p=0.0001) but vBMD (g/cm3) was similar in the two groups (0.16±0.03 vs. 0.16±0.02, p=0.953). Range of motion was similar in elbow, knee and hip in IGHD and CO. Limitation of extension of the elbow was found in 1 IGHD individual and in none of controls. Genu valgum was more frequent in IGHD than CO (9/23 vs. 1 /15, p<0.0001). OA knee score was similar  and hip score was higher in IGHD than CO (1.73±0.36 vs. 0.74±0.11, p=0.003)

Discussion:  Although adult GH-naïve individuals with congenital IGHD have lower areal BMD, they have normal vBMD (more appropriate technique to compare different sized subjects). Our data of normal vBMO in IGHD (of both genders) agree with a previous report in 4 males with a different GHRH-R mutation (2), and with data from subjects with GH resistance (3), suggesting that bone density is not reduced in lifetime congenital IGHD. In contrast, the IGHD subjects present more OA and genu valgum than CO.

Conclusion: Congenital, lifetime IGHD causes joint problems, reduces bone size  but does not reduce vBMD.

1) Maheshwari HG et al. J Clin Endocrinol Metab 88; 2614-2618, 2003. 2) Bachrach LK et al. J Bone Miner Res 1998; 13;415-421.3) De Paula, Clinical Endocrinology (2009) 70, 35–40.


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