Bone densitometric and histomorphometric responses to sequential human parathyroid hormone (1-38) and salmon calcitonin in osteoporotic patients.
Cyclical treatments of osteoporosis utilizing a skeletal Activator of bone remodelling, and sequential therapy with a Depressor to selectively block the resulting phase of osteoclastic resorption have been dubbed 'ADFR' therapy; there is usually a treatment Free interval while the activated bone multicellular units complete the remodelling cycle before the protocol is Repeated. In this report an ADFR protocol was developed in which all patients received synthetic hPTH (1-38) for the first 14 days of a 100 day cycle. Half the patients received no other therapy (Group 1), but were followed closely with repeated vertebral bone mineral measurements over two full cycles. The remaining patients (Group 2) were randomly allocated to receive salmon calcitonin, at an average dose of 79 units per day for a 56 day depressor period immediately following each phase of activation. Detailed bone histomorphometry was performed on iliac biopsies obtained before treatment and at the end of the second cycle (Day 200). In Group 1, the serum alkaline phosphatase (Alk. P'ase) increased by 23 +/- 12% (P less than 0.01) and by 18 +/- 16% (P less than 0.03) of the baseline values following PTH treatment during the first and second cycles, respectively. The overall changes in serum Alk. P'ase across time were significantly less (P less than 0.04) in Group 2; however this parameter also increased by 15 +/- 15% during the first cycle and 8 +/- 6% during the second cycle. Vertebral BMC increased by 13% in Group I (P less than 0.01), but forearm BMC decreased by 11% (P less than 0.05) over the two cycles of therapy. There were no significant changes in bone mineral measurements in Group 2, but the differences between the two groups were not significant. Eighteen paired biopsies were available for histomorphometric analysis. There were no significant changes in static parameters measuring total bone tissue, osteoclastic function or osteoid formation after two cycles of treatment. Individual bone formation rates (surface referent) were not significantly different between the two groups; the pooled data for all biopsies showed a small but insignificant increase from 0.030 +/- 0.018 to 0.035 +/- 0.028 mm3/mm2/day. However there was a significant increase in the activation frequency (the probability of a remodelling event occurring on queiscent cancellous surface) from 13 +/- 7 to 27 +/- 26/day x 10(-4) (P less than 0.05) when calculated for the pooled data from both groups.(ABSTRACT TRUNCATED AT 400 WORDS)
Hodsman
A B
AB
Department of Medicine, Lawson Research Institute, St. Joseph's Health Centre, London, Ontario, Canada.
Steer
B M
BM
Fraher
L J
LJ
Drost
D J
DJ
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001706:Biopsy; D015519:Bone Density; D002116:Calcitonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C035747:parathyroid hormone (1-38); C028815:salmon calcitonin; D002116:Calcitonin; D000469:Alkaline Phosphatase