Atenolol, alone or in combination with PTH, has a modest effect on bone in female C57BL/6J mice

Atenolol is a β1-selective β-adrenergic receptor antagonist (a.k.a. β-blocker) and is under investigation in a clinical trial to prevent osteoporosis in postmenopausal women. The effects of atenolol on rodent bone are unknown, which limits research investigating mechanisms or modeling human treatment effects. However, propranolol, a non-selective β-blocker, has been widely used in rodent models. Propranolol co-treatment with intermittent truncated PTH improves a serum marker of bone formation, P1NP, while blocking the PTH-induced increase in CTX-I-MMP, a serum marker of bone resorption. To determine whether atenolol has similar properties as propranolol during co-treatment, we tested the combined effects of atenolol and PTH in female C57BL/6J mice. Atenolol exposure was confirmed in both serum and marrow at clinically relevant levels. Atenolol had little effect on femoral or L5 vertebra microarchitecture, either on its own or in combination with PTH, which improved trabecular microarchitecture as expected. However, co-treatment with PTH significantly increased P1NP levels past that of PTH alone, suggesting longer treatment may improve bone density by increasing bone formation. In summary, we found little effect of atenolol alone or in combination with PTH, which may be related to relative selectivity of atenolol for β1AR over β2AR, the predominant βAR in bone. Future studies should test whether longer term atenolol may improve microarchitectural parameters with PTH co-treatment.