Growth Hormone Favorably Affects Bone Turnover and Bone Mineral Density in Patients With Short Bowel Syndrome Undergoing Intestinal Rehabilitation

Abstract

Background: Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. Methods: Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. Results: The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels <30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p < .05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. Conclusions: hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.

Adult patients with severe short bowel syndrome received individualized oral diets and were randomized to recombinant human growth hormone (hGH) or placebo to determine effects on bone mineral density (B) and markers of bone turnover. Vitamin D deficiency was common in both groups. After 4 and 12 weeks of therapy, hGH-treated subjects compared to placebo-treated subjects demonstrated increased markers of bone formation (osteocalcin) and bone resorption (N-telopeptide), respectively, indicating an increased rate of bone turnover induced by hGH. At 12 and 24 weeks, there was no change in B vs baseline values in the hGH group however, at 24 weeks there was a modest but significant decrease in B of the femoral neck in the placebo group.

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