A model for investigating the local action of bone-acting agents in vivo: effects of hPTH(1-34) on the secondary spongiosa in the rat.
Cytokines and other local factors are likely to play an important role in bone remodeling. The purpose of this study was to develop an experimental model for evaluating the local action of various hormones and other agents on rat femur trabecular bone in vivo. Through a 1 mm diameter hole (1 mm deep) on the lateral aspect of the distal cortex of a rat femur (0.9 cm above the joint), a polyethylene tube was inserted and glued onto the bone. This tube was connected to a vascular-access-port which was implanted subcutaneously in the hip area of male Sprague-Dawley rats weighing 190-210 g. To evaluate this model, a single 50 microliters injection of 10(-8), 10(-10), or 10(-12) M hPTH(1-34) was given 1 day after catheter implantation and the number of osteoclasts was estimated 30 hours later. Bones were fixed, embedded, and stained with Masson's Trichrome stain and subjected to histomorphometric analysis. The single local parathyroid hormone (PTH) injection caused a dose-dependent increase in osteoclast number from 1.7 +/- 0.3 for phosphate-buffered saline (PBS) controls to 3.4 +/- 0.5, 5.8 +/- 0.9, and 5.4 +/- 1.0/mm for 10(-12), 10(-10), and 10(-8) M PTH, respectively. There was no increase in osteoclast number in the femurs of PBS-injected control rats, in the femurs of sham-operated rats, or in the untreated contralateral femur of the PTH-injected rat. The local injection of hPTH(1-34) did not change serum calcium, serum phosphate, or the urinary phosphate/creatinine ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Takano-Yamamoto
T
T
Department of Bone Biology and Osteoporosis Research, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Rodan
G A
GA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002452:Cell Count / Q000187:drug effects; D003401:Creatine / Q000652:urine; D005269:Femur / Q000166:cytology / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010710:Phosphates / Q000097:blood / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide; D013997:Time Factors
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D019379:Teriparatide; D003401:Creatine; D002118:Calcium