Osteoporosis is the most prevalent bone disease worldwide.4,5 Although several agents to inhibit bone resorption are currently available, iPTH is one of the few clinically approved substances for stimulating bone formation.6 Application of iPTH is limited to a duration of 2 years, after which the levels of bone resorption markers increase and no net gain in bone mass is achievable.46–48 In our current study, we show that Calca-encoded peptides are of crucial importance in regulating the therapeutic effect of iPTH. The gene discussed is CALCA; the disease is osteoporosis.