Primary hyperparathyroidism is characterized by elevated parathyroid hormone (PTH) levels and hypercalcemia, causing bone loss and fragility. PTH activates the PTH receptor (PTH1R), which primarily couples to Gαs, stimulating downstream effectors. Previously, we have seen trabecular anabolic effects of hyperparathyroidism in mice overexpressing Gαs. We hypothesized that increased Gαs protein levels in osteoblasts outcompete β-arrestins binding to PTH1R, leading to reduced signal termination and increased bone formation. In this study, we tested whether β- arrestin2 deletion results in an anabolic response to hyperparathyroidism. While wild-type male mice exhibited a bone catabolic response, female mice were resistant. Contrarily, β-arrestin2 knockout male mice maintained bone whereas female mice exhibited an anabolic response. These results support our hypothesis that arrestin-mediated PTH1R downregulation contributes to bone loss associated with hyperparathyroidism. This offers new insight into the mechanism of bone loss in primary hyperparathyroidism that could be a path for drug therapy.