PTH and hyperparathyroidism: This antagonistic effect might result from direct inhibition of periosteal osteoblast differentiation by PTH receptor activation, and it is consistent with the accumulation of immature osteoblasts with chronic elevation of PTH, such as in severe hyperparathyroidism(43) or in the Col1a1-caPTHR1 transgenic mice.(42,44) This phenomenon might also help explain the failure of PTH to increase bone formation in the periosteal surface in some conditions.(17–19)