SERUM COLLAGEN CROSS-LINKS AS MARKERS OF BONE TURN-OVER DURING GH REPLACEMENT THERAPY IN GROWTH-HORMONE DEFICIENT ADULTS

OBJECTIVES Bone metabolism is an important target for GH replacement t herapy. However, in adults, treatment periods exceeding 12 months are required for a positive effect of GH on bone mineral density. Thus, to detect an early effect of GH on bone, markers of bone turn-over are i mportant. Pyridinoline (PYR) and deoxypyridinoline (DPYR) are well-def ined sensitive markers of bone resorption, but to date only urinary as says have been available. We report the use of a novel assay to measur e changes in serum PYR and DPYR in GH deficient (GHD) adults during GH replacement therapy. STUDY DESIGN The study consisted of a 6-month ra ndomized, double-blind, placebo-controlled study of the administration of GH (Genotropin(R)) (0.25 IU/Kg/week (0.125 IU/kg/week for the firs t four weeks)) followed by a 6-month open phase of GH therapy. PATIENT S Thirty-five GHD adults (17 women; mean age 39.8 years; range 21.1-59 .9) on conventional hormone replacement therapy as required, were stud ied. MEASUREMENTS Bone formation was analysed using serum bone alkalin e phosphatase (BAP) and serum osteocalcin (OC). Bone resorption was an alysed using serum pyridinoline (PYR) and serum deoxypyridinoline (DPY R). Bone mineral density (BMD) was determined by dual energy X-ray abs orptiometry (DEXA). RESULTS After 6 months placebo treatment there wer e no significant changes in any of the bone markers analysed, nor in B MD. In the active arm of the study there was a significant increase in serum OC, BAP, PYR and DPYR (P=0.03, P=0.004, P=0.003 and P=0.01, res pectively), remaining significantly elevated over their baseline level s for the subsequent 6 months of treatment (P=0.04, P=0.009, P=0.003 a nd P=0.04, respectively). No changes were observed in BMD in any of th e groups after 6 months GH treatment. In the active arm of the study, after 12 months GH treatment there was a significant increase in BMD a t both the lumbar spine and femoral neck (P=0.01 for both sites). CONC LUSIONS In summary, the present study confirms that administration of GH treatment to GHD adult patients significantly activates bone remode lling, with the effect of GH both in bone formation and bone resorptio n markers being maximal after 6 months of treatment. The serum assay f or PYR and DPYR has a number of practical and theoretical advantages o ver the urine assay and gave similar results to those previously repor ted for the urine assay.