Abaloparatide, a novel analog of parathyroid hormone‐related protein (PTHrP 1–34), became in 2017 the second osteoanabolic therapy for the treatment of osteoporosis. This study aims to compare the effects of PTH (1‐34), PTHrP (1‐36), and abaloparatide on bone remodeling in male mice. Intermittent daily subcutaneous injections of 80 μg/kg/d were administered to 4‐month‐old C57Bl/6J male mice for 6 weeks. During treatment, mice were followed by DXA‐Piximus to assess changes in bone mineral density (BMD) in the whole body, femur, and tibia. At either 4 or 18 hours after the final injection, femurs were harvested for μCT analyses and histomorphometry, sera were assayed for bone turnover marker levels, and tibias were separated into cortical, trabecular, and bone marrow fractions for gene expression analyses. Our results showed that, compared with PTH (1‐34), abaloparatide resulted in a similar increase in BMD at all sites, whereas no changes were found with PTHrP (1‐36). With both PTH (1‐34) and abaloparatide, μCT and histomorphometry analyses revealed similar increases in bone volume associated with an increased trabecular thickness, in bone formation rate as shown by P1NP serum level and in vivo double labeling, and in bone resorption as shown by CTX levels and osteoclast number. Gene expression analyses of trabecular and cortical bone showed that PTH (1‐34) and abaloparatide led to different actions in osteoblast differentiation and activity, with increased Runx2, Col1A1, Alpl, Bsp, Ocn, Sost, Rankl/Opg, and c‐fos at different time points. Abaloparatide seems to generate a faster response on osteoblastic gene expression than PTH (1‐34). Taken together, abaloparatide at the same dose is as effective as PTH (1‐34) as an osteoanabolic, with an increase in bone formation but also an increase in bone resorption in male mice. © 2019 American Society for Bone and Mineral Research.

E mu-Pim1 transgenic mice expressing a dysregulated Pim1 oncogene in their lymphoid cells were used to test whether exposure to 50 Hz magnetic fields can increase the frequency of malignant lymphoma in mice of a strain predisposed to develop such tumors spontaneously at low incidence. Specific-pathogen-free female mice were allocated randomly into groups of approximately 100 at 6-8 weeks of age and then exposed for 20 h/day for up to 18 months to sinusoidal magnetic fields of 0, 1, 100 or 1000 microT, or 1000 microT pulsed 15 min on and 15 min off. Additional E mu-Pim1 mice were injected with ethylnitrosourea (50 mg/kg body weight) as positive controls for enhanced lymphomagenesis; these yielded a cumulative incidence of lymphoma of 60% in 9 months. A lethal, transgene-dependent renal glomerular disease occurred at a frequency that varied from 9% to 19% among the groups, but the increase was statistically significant only at the 1000-microT exposure. Lymphoblastic and non-lymphoblastic (predominantly follicular) lymphomas were seen in 26 to 35% of the exposed mice, but at no significantly higher incidence than the 29% found in the sham-exposed mice. Hence we conclude that the lymphoma-prone mice did not reveal any tumorigenic effect of long-term exposure to 50 Hz magnetic fields.

Abaloparatide is a peptide analog of parathyroid hormone‐related protein (PTHrP 1–34) and was approved in 2017 as the second osteoanabolic peptide for treating osteoporosis. We previously showed that intermittent abaloparatide is equally as effective as PTH (1–34). This study was designed to compare the catabolic effects of PTH (1–34) and abaloparatide on bone in young female wild‐type mice. Two‐month‐old C57Bl/6J female mice were continuously infused with human PTH (1–34) or abaloparatide at 80 μg/kg BW/day or vehicle for 2 weeks. At euthanasia, DEXA‐PIXImus was performed to assess bone mineral density (BMD) in the whole body, femurs, tibiae, and vertebrae. Bone turnover marker levels were measured in sera, femurs were harvested for micro–computer tomography (μCT) analyses and histomorphometry, and tibiae were separated into cortical and trabecular fractions for gene expression analyses. Our results demonstrated that the infusion of abaloparatide resulted in a similar decrease in BMD as infused PTH (1–34) at all sites. μCT and histomorphometry analyses showed similar decreases in cortical bone thickness and BMD associated with an increase in bone turnover from the increased bone formation rate found by in vivo double labeling and serum P1NP and increased bone resorption as shown by osteoclast numbers and serum cross‐linked C‐telopeptide. Trabecular bone did not show major changes with either treatment. Osteoblastic gene expression analyses of trabecular and cortical bone revealed that infusion of PTH (1–34) or abaloparatide led to similar and different actions in genes of osteoblast differentiation and activity. As with intermittent and in vitro treatment, both infused PTH (1–34) and abaloparatide similarly regulated downstream genes of the PTHR1/SIK/HDAC4 pathway such as Sost and Mmp13 but differed for those of the PTHR1/SIK/CRTC pathway. Taken together, at the same dose, infused abaloparatide causes the same high bone turnover as infused PTH (1–34) with a net resorption in female wild‐type mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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