Changes in extracellular [Ca²⁺] ([Ca²⁺]_e) modulate the function of bone cells in vitro via the extracellular Ca²⁺-sensing receptor (CaR). Within bone microenvironments, resorption increases [Ca²⁺]_e locally. To determine whether enhanced CaR signaling could modulate remodelling and thereby bone mass in vivo, we generated transgenic mice with a constitutively active mutant CaR (Act-CaR) targeted to their mature osteoblasts by the 3.5 kb osteocalcin promoter. Longitudinal micro-computed tomography (µCT) of cancellous bone revealed reduced bone volume and density, accompanied by a diminished trabecular network, in the Act-CaR mice. The bone loss was secondary to an increased number and activity of osteoclasts, demonstrated by histomorphometry of secondary spongiosa. Histomorphometry on the other hand indicates that bone formation rates were unchanged in the transgenic mice. Constitutive signaling of the CaR in mature osteoblasts resulted in increased expression of RANK-L (receptor activator of nuclear factor-B ligand), the major stimulator of osteoclast differentiation and activation, which is the likely underlying mechanism for the bone loss. The phenotype of Act-CaR mice is not due to systemic changes in serum [Ca²⁺] or parathyroid hormone (PTH) levels. We provide the first in vivo evidence that increased signaling by the CaR in mature osteoblasts can enhance bone resorption, and further propose that fluctuations in the [Ca²⁺] within the bone microenvironment may modulate remodeling via the CaR.