Effects of treatment with parathyroid hormone 1-84 on quantity and biomechanical properties of thoracic vertebral trabecular bone in ovariectomized rhesus monkeys.
Osteoporosis is characterized by impaired bone quality leading to increased susceptibility to fracture, particularly of the thoracic spine. However, the lumbar spine is studied most commonly. We investigated the effects of 16 months of treatment with full-length parathyroid hormone (PTH) 1-84 (5, 10, or 25 microg/kg) on bone mineral density (BMD) and on architecture and biomechanical properties of trabecular bone at the thoracic spine of ovariectomized (OVX) adult rhesus monkeys and compared the results with those from the lumbar spine. At baseline, 9 months after surgery, dual-energy X-ray absorptiometric BMD at T9-T12 was 7% lower in OVX than in sham animals. All PTH(1-84) doses increased BMD to sham levels within 7 months. Micro-computed tomography of T10 vertebrae showed that trabecular bone volume and connectivity were higher in PTH(1-84)-treated animals than in sham controls, primarily through a significantly greater trabecular number. Peripheral quantitative computed tomography of trabecular bone cores from T11 and T12 confirmed that PTH(1-84) increased BMD. Compression testing of the cores showed that PTH(1-84) treatment increased stiffness, modulus, yield load, and yield stress to levels significantly greater than in sham animals, with the largest effect in the 10 microg/kg group (35-54% greater than in OVX controls). Thus, PTH(1-84) treatment increased BMD and the biomechanical properties of trabecular bone at the thoracic spine of OVX rhesus monkeys. The 10 microg/kg dose produced the greatest effect on trabecular strength, possibly because the highest dose stimulated bone remodeling excessively. Importantly, the changes observed were similar to those in lumbar vertebrae, thereby validating extrapolation of results from the lumbar to the thoracic spine.
Fox
J
J
NPS Pharmaceuticals, 550 Hills Drive, Bedminster, NJ 07921, USA. jfox@npsp.com
Newman
M K
MK
Turner
C H
CH
Guldberg
R E
RE
Varela
A
A
Smith
S Y
SY
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D019245:Compressive Strength / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004548:Elasticity / Q000187:drug effects; D005260:Female; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D008253:Macaca mulatta; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D013314:Stress, Mechanical; D013904:Thoracic Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D014057:Tomography, X-Ray Computed
D010281:Parathyroid Hormone