Dynamics of bone turnover in children with GH deficiency treated with GH until final height

Abstract

Objective: To examine the dynamics of bone turnover in children with growth hormone deficiency (GHD) during long-term treatment. Design: We longitudinally measured growth velocity and serum concentrations of osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP), and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in 24 patients with GHD during long-term GH treatment until final height (age: 7.7 Ϯ 0.7 and 16.9 Ϯ 0.5 years at baseline and at final height respectively). Results: At baseline, OC, PICP, and ICTP levels were significantly (P < 0.0001) reduced in comparison with prepubertal bone age-matched controls (10.2 Ϯ 2.3 mg/l and 22.5 Ϯ 7.6 mg/l; 187.8 Ϯ 26.2 mg/l and 328.4 Ϯ 74.3 mg/l; 7.7 Ϯ 2.0 mg/l and 14.2 Ϯ 1.3 mg/l respectively). During the first year of treatment mean levels of the bone markers increased significantly (P < 0.0001) with a peak at 12 months. After the first year of treatment, OC and PICP levels progressively declined, whereas ICTP levels remained stable until the final height; in any case, bone marker levels remained significantly higher (P < 0.03-P < 0.0001) than baseline. The change in bone marker levels at 6 and 12 months of treatment with respect to the baseline values was not related to growth rate during long-term treatment or final height. Conclusions:The results show that children with GHD have reduced bone turnover at baseline, and that long-term GH treatment is associated with a stimulation of bone turnover. OC, PICP, and ICTP do not predict growth rate during long-term treatment or final height in children with GHD.

Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency

“…Twenty-four months after cessation of GH treatment, lumbar bone mass had declined in patients but not in controls. These results suggest that in young adults with GHD, GH replacement may be needed to support adequate bone mass accumulation in order to maintain bone mass in adult life (21)(22)(23). Furthermore, it seems likely that adolescents with severe GHD may not have achieved their peak bone mass at adult height, when GH treatment is often discontinued, and that GH may play an important role in the acquisition and maintenance of bone mass during this particular period of bone consolidation (3,(24)(25)(26).…”

“…However, the timing of acquisition of peak bone mass in young adults with GHD is not well researched. In a study of 16 adolescent patients (aged 15-19 years) with isolated GHD, lumbar BMD area (bone mineral content (BMC) corrected for vertebral surface area) and lumbar BMD volume (BMC corrected for vertebral volume) were below the normal mean, and mean values of peak BMD were reduced in patients compared with controls (21). Twenty-four months after cessation of GH treatment, lumbar bone mass had declined in patients but not in controls.…”

Growth and development after hematopoietic cell transplant in children

“…Studies in children with GH deficiency have shown that GH deficiency-associated reduced bone turnover is reversed with GH therapy. 27 Because the foundation for skeletal health is established in childhood, prevention of decreased bone mineral density begins by optimizing gains in bone mineral acquisition throughout childhood. Although bone health among children after HCT has not been well studied, one report shows that the effect of GH and bisphosphonate therapy on bone mineral density resulted in an improvement in bone mineral density among those treated with GH and bisphosphonate compared to those who received GH without bisphosphonate.…”

Bone development during GH and GnRH analog treatment

“…In children and adolescents with GHD, BMD assessed by DEXA and bone turnover are significantly reduced (40), reflecting decreased bone modeling and remodeling (41), because of delayed bone maturation or absence of GH anabolic activity (42).…”