Abstract
In rodent osteoporosis models such as ovariectomized (OVX) rats, intermittently administered
human parathyroid hormone (hPTH) has an anabolic effect in vertebrae and long bones.
In the present experiments, subcutaneously injected hPTH(1 - 34) or hPTH(1 - 84) dose-
and time-dependently increased bone mineral density (BMD) as measured by dual energy
X-ray absorptiometry in mandibles, L2 to L4 vertebrae and femurs of such rats. The
highest dose (15.9 nmol/kg, s. c.) of either peptide given four times weekly for 10
weeks completely reversed the effects of overiectomy on BMD. Significant elevation
in lumbar BMD after 10 weeks was observed with hPTH(1 - 34) or hPTH(1 - 84) at 1.1
nmol/kg, whereas hPTH(1 - 34) at 1.1 and 4.2 nmol/kg significantly increased BMD of
the whole bone and the metaphysis of the femur and the diaphysis of the bone, respectively.
In contrast, significant effects of hPTH(1 - 84) administration on BMD increase in
the femur were observed at 4.2 and 15.9 nmol/kg in the whole bone and the metaphysis,
and in the diaphysis, respectively. Maxillary molar extraction left mandibular BMD
in rats with intact ovaries unchanged, but significantly decreased mandibular BMD
in OVX rats. Administration of hPTH(1 - 84) for 10 weeks in OVX rats without or with
extraction significantly increased BMD in the mandibular molar region at doses of
15.9 and 4.2 nmol/kg, respectively, indicating that efficacy was increased by extraction.
A significant BMD increase in the molar region in OVX rats with extraction occurred
at only 1.1 nmol/kg of hPTH(1 - 34) and 4.2 nmol/kg of hPTH(1 - 84). Also, BMD of
the ramus region was increased by administration of both peptides to a lesser extent
than that of the molar region in these rats. Thus, intermittent administration of
hPTH, especially hPTH(1 - 34), has an anabolic effect on bone, particularly alveolar
bone. Such treatment may increase alveolar bone mass in postmenopausal women with
osteoporosis.
Key words
Intermittent Administration - Bone Mineral Density - Bone Formation - Osteoporosis
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