Effects of single and concurrent intermittent administration of human PTH (1-34) and incadronate on cancellous and cortical bone of femoral neck in ovariectomized rats.
The purpose of this study is to determine the efficacy of concurrent treatment with human parathyroid hormone, hPTH (1-34), and bisphosphonate (incadronate) in augmenting cortical and cancellous bone mass of femoral neck in ovariectomized (OVX) rats. Forty-eight 11-week-old female Sprague-Dawley rats were divided into eight groups (six animals in each group). The baseline control group was killed at the beginning of the experiment, at 11 weeks of age. An ovariectomy was performed in thirty rats and twelve rats were subjected to a sham surgery. OVX rats were untreated for the first four weeks of postsurgery to allow for the development of moderate osteopenia. These animals were then subjected to various treatments with either PTH, incadronate, or PTH+ incadronate for a period of 4 weeks. Right proximal femora (femoral necks) were used for bone histomorphometry. After OVX 8 weeks, there was a significant decrease in cancellous bone mass and cortical bone area of femoral neck in the OVX rats when compared to the sham control rats. In OVX rats treated with PTH alone or PTH+ incadronate were completely restored lost cancellous and cortical bone mass of femoral neck by increase bone formation. The bone formation parameters (OS/ BS, MS/BS) and bone turnover (BFR/BV) seen with PTH plus incadronate were similar to those seen with PTH treatment alone. This indicates that incadronate did not blunt the anabolic action of PTH when used concurrently. Our results suggest the followings: 1) the femoral neck of OVX rats is a suitable sample site for preclinical studies of the prevention of bone loss induced by estrogen depletion; 2) concurrent use of incadronate did not blunt the anabolic effect of PTH; 3) concurrent treatment showed the best results in restoring cancellous and cortical bone mass; and 4) it had additional benefits for bone strength independent of that achieved by the increase in bone mass.
Zhang
L
L
Department of Orthopedic Surgery, Niigata University School of Medicine, Japan.
Endo
N
N
Yamamoto
N
N
Tanizawa
T
T
Takahashi
H E
HE
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D005272:Femur Neck / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D004164:Diphosphonates; D019379:Teriparatide; C071542:cimadronate