Intermittent PTH treatment has been used as both an osteoanabolic treatment in osteoporosis and a hormone replacement in hypoparathyroidism for many years. This scoping review compiles and reinterprets studies using histomorphometry supported by bone turnover markers to investigate the elusive cellular effect of intermittent PTH treatment locally within the bone, while illuminating knowledge gaps. Intermittent PTH increases both osteoclast and osteoblast activity within the first 6 months of treatment. Based on the combination of systemic bone turnover markers and histomorphometry we suggest that in osteoporosis, the activity of the individual osteoclast increases within the first 18 months of treatment. During the initial 6 months, osteoblast activation increases bone formation, whereafter bone formation returns to baseline after 7-18 months of treatment. Based on the studies available after 24 months of treatment, more osteoclasts populate the bone surfaces, but the individual osteoclast may potentially be less active. At the same time, osteoblastic bone formation appears to be reactivated. In hypoparathyroidism, treatment up to 72-120 months increases bone formation and normalizes it to a level of matched healthy controls, while the osteoclast remains largely uninvestigated. The increase in bone forming surfaces in both osteoporosis and hypoparathyroidism may partly be achieved by rejuvenating arrested eroded surfaces accumulated during disease. Contrary to early beliefs, modeling-based bone formation (MBF) is not a major contributor to PTH-induced bone formation. Rather osteoclast-initiated bone formations such as remodeling-based bone formation (RBF) and overflow remodeling-based bone formation (oRBF) are the predominate modes of bone formation, underlining a need for further investigations into possible effects of previous osteoclast-inhibiting anti-resorptive treatment.
Keywords: Histomorphometry; Hypoparathyroidism; Modeling; Osteoporosis; Parathyroid hormone; Remodeling.
© 2025. The Author(s), under exclusive licence to the International Osteoporosis Foundation and the Bone Health and Osteoporosis Foundation.