Abstract
To investigate whether the administration frequency of parathyroid hormone (PTH) is associated with the development of cortical porosity, this study established 15 dosage regimens of teriparatide [human PTH(1–34), TPTD] with four distinct concentrations and four distinct administration frequencies of TPTD to 16-week-old ovariectomized rats. Our analyses demonstrated that the bone mineral density, mechanical properties, and bone turnover were associated with the total amount of TPTD administered. Our observations further revealed that the cortical porosity was markedly developed as a result of an increased administration frequency with a lower concentration of total TPTD administration in our setting, although the highest concentration also induced cortical porosity. Deconvolution fluorescence tiling imaging on calcein-labeled undecalcified bone sections also demonstrated the development of cortical porosity to be closely associated with the bone site where periosteal bone formation took place. This site-specific cortical porosity involved intracortical bone resorption and an increased number and proximity of osteocytic lacunae, occasionally causing fused lacunae. Taken together, these findings suggested the involvement of local distinctions in the rate of bone growth that may be related to the site-specific mechanical properties in the development of cortical porosity induced by frequent and/or high doses of TPTD.
Highlights
The effects of parathyroid hormone (PTH) on rat bone metabolism were first observed in the early 1900s.1–3 Since the achievement of the chemical synthesis of human PTH (1–34) in the 1970s, studies have attempted to define the detailed mechanism of this hormonal action.[4]
Effects of TPTD administration regimen in ovariectomized. In total (OVX) rats on bone mineral density (BMD), mechanical properties, and systemic bone markers To analyze the effect of the TPTD administration frequency on bone quality in OVX rats, we established four administration schedules: three times a week (3/w), once a day (1/d), twice a day (2/d), and three times a day (3/d) with four distinct TPTD doses: 0, 1.2, 6, and 30 μg·kg − 1 for 4 weeks (Table 1)
This study used a standard OVX rat model of postmenopausal osteoporosis to examine the effects of TPTD at distinct dosage and frequency of administration on BMD, mechanical properties of bone, systemic bone formation and resorption markers, and development of cortical porosity
Summary
The effects of parathyroid hormone (PTH) on rat bone metabolism were first observed in the early 1900s.1–3 Since the achievement of the chemical synthesis of human PTH (1–34) in the 1970s, studies have attempted to define the detailed mechanism of this hormonal action.[4]. The effects of parathyroid hormone (PTH) on rat bone metabolism were first observed in the early 1900s.1–3. Since the achievement of the chemical synthesis of human PTH (1–34) in the 1970s, studies have attempted to define the detailed mechanism of this hormonal action.[4] The anabolic effect of PTH on the skeleton in post-menopausal osteoporosis reported by Reeve et al[5] was the first clinical application. PTH is well known to exert its anabolic effects on bone through promoting the proliferation, differentiation and survival of bone-forming osteoblasts, which concomitantly induce the differentiation of osteoclasts, thereby promoting bone resorption.[6] The balance between these anabolic and catabolic actions of PTH administration is thought to be defined by the blood concentration of PTH, the exact molecular and cellular mechanisms underlying these phenomena remain controversial. The intermittent exposure of PTH increases bone formation over resorption, whereas the continuous infusion of PTH stimulates bone resorption over formation, causing a net loss in bone mass.[7,8]
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