Skeletal Effects of Parathyroid Hormone Infusion in Ovariectomized Rats With or Without Estrogen Repletion

• Published in: Journal of bone and mineral research 2000-04, Vol.15 (4), p.740-746
• Main Authors: Shen, V., Birchman, R., Wu, D.‐D., Lindsay, R.
• Format: Article
• Language: English
• Subjects: Amino Acids - urine; Animals; Biological and medical sciences; Bone Density; bone mineral density; Bones, joints and connective tissue. Antiinflammatory agents; Calcium - blood; estrogen; Estrogens - administration & dosage; Female; Femur - drug effects; Femur - physiology; hyperparathyroidism; Infusion Pumps; Medical sciences; Ovariectomy; parathyroid hormone; Parathyroid Hormone - administration & dosage; Peptide Fragments - administration & dosage; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; turnover markers
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2000.15.4.740

We employed skeletally matured rats to study changes in biochemical markers of bone turnover, bone mineral density (BMD), and bone biomechanics produced by continuous elevation of parathyroid hormone (PTH) in estrogen‐deplete and ‐replete rodents. Ninety‐six 7‐month‐old virgin female rats were divided randomly into 12 groups (n = 8) and treated as follows. One group was killed on the day of surgery. The remaining groups were either bilaterally ovariectomized (Ovx) or sham‐operated and left untreated for 8 weeks, at which point, two groups, one sham and one Ovx, were killed. The remaining nine groups were treated for 2 weeks or 4 weeks. One sham and two Ovx groups received subcutaneous implants of Alzet miniosmotic pumps with vehicle for PTH. Two Ovx groups were given pumps with vehicle as well as a subcutaneous implant of 17β‐estradiol, which delivered 10 μg/kg per day. Two Ovx groups were implanted with rat PTH(1–34) in Alzet miniosmotic pumps, which delivered 30 μg PTH/kg per day. Two Ovx groups were implanted with both estradiol pellets and PTH‐loaded pumps. One group of Ovx animals from each treatment was killed after 2 weeks and the other after 4 weeks. Biochemical markers of bone turnover, serum osteocalcin and urinary free pyridinoline, BMD, and mechanical strength of excised bones were measured. As expected, there was a significant increase in N‐terminal PTH and serum calcium levels in all PTH infusion groups. Both serum osteocalcin and urinary pyridinoline showed a rapid increase within the first 2 weeks of the PTH infusion and remained elevated at week 4. In estrogen‐replete groups, osteocalcin increased by week 2 of PTH infusion but pyridinoline did not increase until week 4. BMD of the distal and proximal femur showed the expected decrease 8 weeks after ovariectomy but did not exhibit any further changes during the 4 weeks of treatment with vehicle. Four weeks of PTH infusion in Ovx animals resulted in BMD loss at the midshaft, distal, and proximal regions of the femur. Estrogen repletion by itself, beginning 8 weeks after ovariectomy, produced no change in BMD at any site when compared with from Ovx vehicle‐treated rats. Estrogen repletion in PTH‐infused Ovx animals resulted in significant improvements of BMD comparable with sham‐operated animals at all three femoral regions. The indentation test at the cancellous bone of the distal femur, three‐point bending test at the midshaft femur, and cantilever bending test at the femoral neck showed th