Full 24-month treatment course with daily teriparatide: a mechanistic insight

Osteoporosis Therapy: Bone Modeling during Growth and Aging

“…As discussed recently, daily or weekly treatment with teriparatide would stimulate modeling-based bone formation (11, 23). Bone modeling also seems to be stimulated by daily treatment with abaloparatide, an investigational agent (Table 1).…”

“…This is compatible with binding of abaloparatide to a G protein-dependent conformation of parathyroid hormone type 1 receptor with higher affinity but more transiently than teriparatide (25) and abaloparatide-induced increases in trabecular thickness and total area of cortical bone (26) and can reasonably explain greater increases in areal bone mineral density (BMD) at the femoral neck and total hip after daily treatment with abaloparatide versus teriparatide for 6 months (24). Accordingly, it is possible to speculate that, when teriparatide (20 μg/day) and abaloparatide (80 μg/day) are injected daily, the improvement of bone fragility could be faster by abaloparatide but better for longer duration by teriparatide (23), and abaloparatide rather than teriparatide might be more suitable for use in combination with denosumab (27). Nevertheless, both agents would not be used for children due to carcinogenicity in animals, though clinical experience with teriparatide has not presented such possibility in adults (28); to our knowledge, the use of teriparatide has been reported in a limited number of children with hypoparathyroidism (29), but not with osteoporosis.…”

TGFβ1+CCR5+ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice

“…Osteoporosis, the most common bone disease in aging humans, is characterized by decreased bone mass and strength due to increased osteoclastic bone resorption and decreased osteoblastic bone formation, leading to increased fracture risk, morbidity and mortality 7 . Treatment includes anti-resorptive and anabolic drugs 8,9 ; the former have side effects that now limit patients' willingness to take them 10 , and the latter can be given for only 2 years to patients with severe osteoporosis 11,12 , after which bone loss accelerates 13 . Thus, there a growing need to develop new treatments, based on better understanding of the molecular mechanisms causing bone loss.We reported that during aging: RANKL, an essential osteoclastogenic cytokine 14 , stimulates bone resorption in part by degrading TNF…”