Expansion of the osteocytic lacunar-canalicular system involved in pharmacological action of PTH revealed by AI-driven fluorescence morphometry in female rabbits.

Osteoporosis is an age-related disorder that is characterized by reduced bone mass. Its prevention and treatment are important healthcare issues for maintaining social activity in aged societies. Although bone fractures mostly occur at sites of weakened cortical bone, pathophysiological and pharmacological evaluations of bone mass have tended to be predominantly assessed in trabecular bone.

Teriparatide Improves Bone and Lipid Metabolism in a Male Rat Model of Type 2 Diabetes Mellitus.

Osteoporosis is a complication of diabetes mellitus (DM). The pathology of diabetic osteoporosis is distinct from postmenopausal osteoporosis, and there are no specific treatment guidelines for diabetic osteoporosis. In the current study, this issue was addressed by evaluating the effect of osteoporosis medications, such as the anabolic agent PTH [teriparatide (TPTD)] and the antiresorptive agents calcitonin [elcatonin (ECT)] and bisphosphonate [risedronate (RIS)], on bone metabolism as well as on glucose and lipid metabolism in spontaneously diabetic Torii (SDT) fatty rats, which are a model of type 2 DM (T2DM).

Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats.

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.

Acute development of cortical porosity and endosteal naïve bone formation from the daily but not weekly short-term administration of PTH in rabbit.

Teriparatide [human parathyroid hormone (1-34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity.

Increased cortical porosity is associated with daily, not weekly, administration of equivalent doses of teriparatide.

Introduction: The pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling.

Short-term intermittent administration of parathyroid hormone facilitates osteogenesis by different mechanisms in cancellous and cortical bone.

Intermittent administration of human parathyroid hormone (1-34)[hPTH(1-34)] induces anabolic action on the bones. To understand the mechanism underlying the early phase of hPTH(1-34)-induced anabolic action, we investigated the expression profiles of osterix and sclerostin after short-term intermittent administration of hPTH(1-34) using immunohistochemistry in adult rats. In the cancellous bone, hPTH(1-34) administration greatly increased the number of osterix-positive cells in the bone marrow on day 1, but the cells gradually decreased on days 3 and 5.

Early Effects of Single and Low-Frequency Repeated Administration of Teriparatide, hPTH(1-34), on Bone Formation and Resorption in Ovariectomized Rats.

Intermittent repeated administration of teriparatide (TPTD) has potent anabolic effects on bones in vivo. However, TPTD has both anabolic and catabolic effects on osteoblasts in vitro, and the mechanisms underlying its promotion of bone formation are unclear. This study aimed to elucidate the time-dependent changes in bone formation and resorption by examining changes in bone turnover markers and bone tissue over time after TPTD administration with low frequency in ovariectomized rats.

Comparison of treatment effects of teriparatide and the bisphosphonate risedronate in an aged, osteopenic, ovariectomized rat model under various clinical conditions.

Teriparatide and bisphosphonates are osteoporosis medications that increase bone mineral density (BMD) and prevent fracture, but each has a different mechanism of action. Teriparatide promotes bone formation, while bisphosphonates suppress bone resorption. In the clinical setting, however, drug selection is not always tailored to the particular clinical condition of the patient or mechanism of action of the drug.

Differences in vertebral, tibial, and iliac cancellous bone metabolism in ovariectomized rats.

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively.

Three-times-weekly administration of teriparatide improves vertebral and peripheral bone density, microarchitecture, and mechanical properties without accelerating bone resorption in ovariectomized rats.

Daily and weekly administration of teriparatide (PTH1-34) reduces the risk of osteoporotic bone fractures. However, their effects on markers of bone formation and bone resorption differ. These results indicate that the dosing frequency of teriparatide may affect bone metabolism and bone structure, with different effects on bone strength.

[Effects of parathyroid hormone on bone metabolism : differences between intermittent and continuous treatment].

Numerous animal experiments and human studies have shown that intermittent injection of parathyroid hormone (PTH) exerts anabolic effects by increasing bone mass, whereas continuous PTH treatment decreases the bone mass. Thus, PTH has diverse effects on bone metabolism depending on the mode of administration. Several reports suggested that the duration of the serum concentration of PTH above the baseline level of endogenous PTH is a critical factor in regulating such anabolic and catabolic actions on the bone mass.

[Therapeutic agents for disorders of bone and calcium metabolism: Weekly subcutaneous injection of teriparatide.].

Daily subcutaneous injection of parathyroid hormone (1-34) (teriparatide; TPTD), which is widely used regimen for osteoporotic patients in many countries, exerts strong action on increment of bone volume and prevention of fracture, but activated osteoclastic bone resorption might also occur in this regimen. In contrast, once weekly subcutaneous injection of TPTD, which is being developed in Japan, efficiently increase bone mass by stimulating bone formation without apparent bone resorption. Recent study demonstrated that weekly injection of TPTD increase bone strength in primates by improving bone mass, bone structure and bone quality.