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Bone Status and Fracture Prevalence in Russian Adults with Childhood-Onset Growth Hormone Deficiency

Katholieke Universiteit Leuven (R.B., J.N.), Laboratory of Experimental Medicine and Endocrinology, B-3000 Leuven, Belgium; Eli Lilly & Co. (E.K.), Kobe, Japan; Eli Lilly & Co. (A.F.A.), Florence, Italy; Endocrinological Research Centre (O.B., E.N., O.C., V.P., I.D.), Moscow, Russia; PSI Ltd. (E.S.), St. Petersburg, Russia; and State Research Centre (A.B., V.O.), Institute of Biomedical Problems, Russian Academy of Sciences, Space Physiology Department, Moscow, Russia

Address all correspondence and requests for reprints to: Roger Bouillon, Legendo, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: Roger.Bouillon{at}med.kuleuven.ac.be.

The consequences of lifelong untreated childhood-onset GH deficiency (COGHD) on adult bone and especially fracture prevalence are largely unknown due to the lack of data on long-term outcome of untreated patients. Therefore, we studied adult Russian patients (n = 66; 28 females and 38 males) with idiopathic GH-untreated COGHD. Patients had isolated GH deficiency (IGHD; n = 18, age 23 ± 10 yr) or multiple pituitary hormone deficiency (MPHD) with open (OMPHD; n = 27, age 23 ± 5 yr) or closed growth plates (CMPHD; n = 21, age 55 ± 12 yr). Bone mineral content (BMC) and bone mineral density (BMD) values were compared with 821 normal Russian controls. Fracture prevalence was ascertained from medical history and compared with similar data from 333 normal controls.

Height SD score was –4.6 (range, –1.8 to –8.1). This represents 82% of the height of normal Russian adults. BMC of the lumbar spine, femoral neck, and total body of patients with IGHD was 54, 71, and 59%, respectively, of that of age- and sex-matched controls (all P < 0 0.001). A similarly decreased BMC (42–69% of expected values) was found for all bone regions of patients with both OMPHD and CMPHD. Mean areal BMD measurements (g/cm²) varied (Z scores between –1.8 and –3.0), but the calculated true bone density (g/cm³) was normal in patients with IGHD or CMPHD and only slightly decreased (Z score, –0.8) in patients with OMPHD. Lifetime low-energy fracture prevalence was normal in patients with IGHD but substantially exceeded the expected prevalence in OMPHD (odds ratio of fracture = 3.0; 0.6 fractures per patient; P < 0.0001) or CMPHD patients (odds ratio for fracture = 7.4; 2.2 fractures per patient; P < 0.0001).

In conclusion, IGHD and MPHD of childhood onset very substantially impair adult height and BMC. Although areal BMD is frankly decreased, volumetric bone density is unaffected, but nevertheless, the fracture prevalence in patients with MPHD is markedly increased. These observations demonstrate that not only volumetric density but also bone mass and shape are major determinants of bone strength.

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