Biochemical responses to sequential human parathyroid hormone (1-38) and calcitonin in osteoporotic patients.
Parathyroid hormone (PTH) has been proposed as a skeletal activator for cyclical protocols of treatment for osteoporosis; among several potential drugs that might serve to depress the subsequent phase of osteoclastic bone resorption, calcitonin is the most selective. Twenty patients aged 50-78 years were enrolled in a study of their biochemical responses during a 14-day activation cycle with synthetic hPTH 1-38, given as a subcutaneous injection of 400 IU/day; half the patients were randomly allocated to receive a subsequent 56-day depressor cycle with calcitonin in a dose of 100 U/day, while the remainder received no further treatment. All patients received an initial 24-h intravenous infusion of hPTH 1-38 (0.5 U/kg/h) to evaluate the PTH-dependent renal synthesis of 1,25(OH)2D. Serum calcium increased from 2.20 +/- 0.07 mmol/l to 2.56 +/- 0.16 (P less than 0.005) during PTH infusion, but was not significantly different from baseline during intermittent treatment. Baseline concentrations of serum 1,25(OH)2D were 22.8 +/- 8.2 pg/ml, increased to 52.2 +/- 25.1 (P less than 0.005) during infusion and remained significantly higher than baseline after 14 days intermittent therapy (33.1 +/- 19.4, P less than 0.05). Gastrointestinal absorption of 45Ca, as represented by alpha (peak fractional absorption/h), increased from 0.397 +/- 0.173 to 0.552 +/- 0.210 (P less than 0.01) during hPTH 1-38 therapy and was moderately correlated with the increment in serum 1,25(OH)2D levels (r = 0.5, P less than 0.03). Daily calcium excretion was significantly increased above baseline during hPTH 1-38 therapy, but there were no correlations between changes in urinary calcium, alpha or serum 1,25(OH)2D levels. Baseline fasting urinary excretion of OH-proline increased during hPTH 1-38 treatment from 30.5 +/- 13.9 mol/mmol creatinine to 43.4 +/- 17.5 immediately after hPTH 1-38 infusion (P less than 0.025), and mean excretion was persistently higher than baseline during intermittent treatment; the increased urine calcium and OH-proline excretion are consistent with PTH-induced activation of bone resorption. Serum alkaline phosphatase and osteocalcin levels increased significantly during a 90-day period of observation after the hPTH 1-38 cycle, which is consistent with increased osteoblast activity in association with coupled bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)
Hodsman
A B
AB
Department of Medicine, St. Joseph's Health Centre, London, Ontario, Canada.
Fraher
L J
LJ
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D002116:Calcitonin / Q000008:administration & dosage / Q000627:therapeutic use*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002132:Calcium Radioisotopes; D000242:Cyclic AMP / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000188:drug therapy*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D010710:Phosphates / Q000097:blood / Q000652:urine
D002132:Calcium Radioisotopes; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; C035747:parathyroid hormone (1-38); D015675:Osteocalcin; D002116:Calcitonin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002117:Calcitriol; D006909:Hydroxyproline; D002118:Calcium