In preclinical animal studies:Abaloparatide helped build bone1
Abaloparatide, a PTHrP(1-34) analog, affected both aspects of bone strength, including BMD and quality1,2
Abaloparatide maintained or improved bone quality at all skeletal sites evaluated and did not cause any mineralization defects in animal models of postmenopausal osteoporosis1
*Bone microarchitecture can be understood in terms of trabecular architecture (thickness, orientation, spacing of the trabeculae, and the extent to which the trabeculae are interconnected) and cortical thickness and integrity.3
Abaloparatide is a PTHrP(1-34) analog1
Differences in the amino acid sequence of abaloparatide and hPTHrP(1-34) are indicated by highlighted circles.
In addition, abaloparatide is 41% homologous to hPTH(1-34)1
Specifically designed to build bone7
Abaloparatide demonstrated 1600-fold-greater selectivity to the receptor conformation that drivesbone formation (RG) than to the receptor conformation that drives bone resorption (R0)7
In this study, PTHrP was 110x more selective and PTH was 12x more selective to RG than R0.
Data based on an in vitro study examining the binding of ABL (abaloparatide), PTH(1-34), PTHrP(1-36), and LA-PTH (long-acting PTH)to 2 distinct PTHR1 conformations (RG and R0) as well as the associated cAMP signaling and duration of response.7
See how TYMLOS stimulated bone turnover markers
References: 1. TYMLOS® [prescribing information]. Waltham, MA: Radius Health, Inc; 2020. 2. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785-795. 3. Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther. 2005;27(1):1-11. 4. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). A one-letter notation for amino acid sequences. Eur J Biochem. 1968;5:151-153. 5. National Center for Biotechnology Information. Parathyroid hormone-like hormone [Homo sapiens]. https://www.ncbi.nlm.nih.gov/protein/AAH05961.1. Accessed March 26, 2019. 6. Pioszak AA, Parker NR, Gardella TJ, Xu HE. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J Biol Chem. 2009;284(41):28382-28391. 7. Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ. Binding selectivity of abaloparatide for PTH-type-1-receptor conformations and effects on downstream signaling. Endocrinology. 2016;157(1):141-149.