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Osteocytes orchestrate bone resorption and bone formation by controlling osteoclast and osteoblast activity. On the other hand, osteocytes secret FGF23 (fibroblast growth factor 23), FGF23 acts on the kidney to control phosphate homeostasis. Sclerostin is also released from osteocytes and it regulated osteoblast activity through Wnt/β-catenin pathway. Therefore, an antibody that targets sclerostin is currently in phase- III clinical trials for the treatment of osteoporosis and it is expected as new therapeutics.

Osteoporosis is a disorder of bone formation and resorption balance. Advances in our knowledge of the molecular mechanisms of bone formation and resorption led to promising therapeutic targets for osteoporosis. In the novel biological drugs, denosumab, a monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL) has been clinically applied by positive effect on bone mineral density, negative effect on bone resorption, preventive effect on fragility fractures and safety. Odanacatib, a cathepsin K inhibitor is drawing attention as an antiresorptive drug which has lower bone resorption potency than bisphosphoneate. On the other hand, BHQ-880, an anti-Dickkopf-1 (Dkk-1) antibody and romosozumab (AMG-785) , an anti-sclerostin antibody which activate Wnt/β-catenin signaling pathway are drawing attention as bone formation accelerators with no bone resorption acceleration. Clinical studies of these drugs are now ongoing and their clinical applications are expected.

Daily subcutaneous self-injection and weekly subcutaneous injection formulas of teriparatide are available as anabolic agents in Japan. These injection formulas are expected to serve as a new treatment choice for high fracture-risk patients with osteoporosis. In addition, studies using new anabolic agents such as PTHrP, calcilytics, and Wnt inhibitor antagonists/antibodies are under way to develop new anabolic agents. These agents may become new treatment drugs for osteoporotic patients especially with low bone turnover.

Bone formation is the key for successful dental treatments including periodontal tissue regeneration osseointegration of implant placement in which new alveolar bone formation is mandatory. Parathyroid hormone (PTH) is a peptide hormone containing 84 amino acids. Accumulated results show that intermittent PTH administration increases bone mass. Accordingly, recombinant N-terminal fragment of human PTH (1-34) , Teriparatide, is used for the treatments of osteoporosis worldwide. It is, therefore, expected that PTH has the potential to be a new therapeutic intervention for oral diseases that require increased bone remodeling and new bone formation.

Sclerostin is a secreted protein from osteocytes that inhibits Wnt signaling. Wnt signalling plays important roles in osteoblastic differentiation hence bone formation. Therefore, inhibition of sclerostin promotes bone formation. A monoclonal antibody has been generated against sclerostin, which has been shown to stimulate bone formation and increase bone volume in rodents and primates. Preliminary data on human showed this antibody increases markers for bone formation. Clinical phase 2 study using this antibody in postmenopausal osteoporosis was initiated in 2009, of which results are anticipated.

Wnt signal has been known to play various roles in many organ from the beginning of embryogensis. Its role in bone metabolism has also been investigated and established. Lipoprotein receptor-related protein 5 (LRP5) is one of the important molecules in wnt signal pathway whose point mutations are related to both bone loss and excessive bone formation. Wnt signal is involved in the action of sclerostin which was found as a gene for osteosclerosis, one of the diseases of excessive bone formation. Wnt signal is keeping the position as an important research target for normal and pathological bone formation.

Parathyroid hormone (PTH) has clinically appeared as a bone anabolic reagent in Japan. Local or systemic factors produced by various cells are involved in the bone anabolic action of PTH. Insulin-like growth factor-1 and fibroblast growth factor 2 are included in them. Although the significance of canonical Wnt signaling has been noted as bone anabolic signal, recent reports indicate that an activation of Wnt signaling through several proteins, such as Dkk1 and sclerostin, are related to the bone anabolic action of PTH.

Osteocytes produce DMP1 (dentin matrix protein 1), FGF23 (fibroblast growth factor 23) and sclerostin. FGF23 is a phosphate-regulating hormone that links bone to kidney. DMP1 is a matrix protein that is involved in mineralization. Patients with DMP1 mutations exhibit increased FGF23 and hypophosphatemia, suggesting that DMP1 negatively regulates FGF23 in osteocytes. Sclerostin is secreted by osteocytes and negatively regulates osteoblastic function, and its neutralizing antibody is being developed as a new treatment for osteoporosis. A mouse model that enables targeted ablation of osteocytes tells us about the physiologic and pathologic functions of osteocytes in regulating bone remodeling in response to mechanical environment.

The Wnt signaling pathway has recently been demonstrated to play an important role in regulation of bone formation. LRP5 is thought to signal through the canonical Wnt pathway. In humans, LRP5 loss-of-function mutations lead to low bone mass with fractures, while LRP5 gain-of-function mutations lead to high bone mass, thus identifying LRP5 as an important regulator of bone mass. Patients with sclerosteosis have a severe skeletal disorder with progressive bone overgrowth due to a loss of function of the SOST gene, which implicates its role as a suppressor of bone formation. Recent study revealed that SOST is a BMP antagonist with unique ligand specificity, negatively regulating bone formation by repressing BMP-induced osteoblast differentiation or function or both.