Abaloparatide, sold under the brand name Tymlos among others, is a parathyroid hormone-related protein (PTHrP) analog medication used to treat osteoporosis. It is an anabolic (i.e., bone growing) agent. In 2017, it was approved to treat postmenopausal osteoporosis in the United States. Medical uses Abaloparatide is indicated to treat postmenopausal women with osteoporosis who are at high risk of bone fractures. Side effects The most common side effects reported by more than 2% of clinical trials subjects are hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain and vertigo. Preclinical studies revealed that abaloparatide systemic daily administration leads to a dose- and time-dependent increase in the incidence of osteosarcoma in rodents. However, whether abaloparatide-SC will cause osteosarcoma in humans is unknown. Thus, the use of abaloparatide is not recommended for individuals at increased risk of osteosarcoma. Additionally, its use is not advised for more than 2 years during a patient's lifetime. Pharmacology Abaloparatide is 34 amino acid synthetic analog of PTHrP. It has 41% homology to parathyroid hormone (PTH) (1-34) and 76% homology to parathyroid hormone-related protein (PTHrP) (1-34). It works as an anabolic agent for the bone, through selective activation of the parathyroid hormone 1 receptor (PTH1R), a G protein-coupled receptor (GPCR) expressed in the osteoblasts and osteocytes. Abaloparatide preferentially binds the RG conformational state of the PTH1R, which in turn elicits a transient downstream cyclic AMP signaling response towards to a more anabolic signaling pathway. History Preclinical studies Abaloropatide was invented by Jesse Z. Dong at Ipsen. It was known as BIM-44058 during pre-clinical studies and as BA058 while under clinical development. The anabolic effects of abaloparatide on bone were demonstrated in two preclinical studies conducted in ovariectomized rats. Both studies showed increased cortical and trabecular bone volume and density, and trabecular microarchitecture improvement in vertebral and nonvertebral bones after short-term and long-term daily subcutaneous injection of abaloparatide compared to controls. Recent studies indicated a dose-dependent increased in bone mass and strength in long-term abalorapatide treatment. However, it was also found that prolonged abalorapatide-SC treatment leads to increased incidence of osteosarcoma. To date, there is no evidence for increased risk of bone tumors due to prolonged systemic administration in humans. Based on preclinical data, the FDA does not advised the use of abaloparatide-SC for more than 2 years, or in patients with history of Paget disease and/or other conditions that exacerbates the risk of developing osteosarcoma. Clinical Trials