N-MID, P1NP, ß-CTX, and phosphorus in adolescents with condylar resorption.

OBJECTIVE: Condylar resorption (CR) is a temporomandibular joint disease that causes various physical or functional defects. We aimed to find the association between CR and bone metabolism levels. STUDY DESIGN: In this study, we recruited patients visiting the Orthodontic Clinic at Shanghai Ninth People's Hospital from January 2020 to September 2021. Patient characteristics, magnetic resonance imaging examination results, bone mineral density (BMD), Z-score, bone turnover markers, minerals, and hormones were collected and analyzed. RESULTS: The 89 participants were divided into CR (n = 46) and normal (n = 43) groups. Univariate logistic regression showed that N-terminal mid-fragment of osteocalcin (N-MID), procollagen type 1 N-terminal propeptide (P1NP), ß-C-terminal telopeptide of type 1 collagen (ß-CTX), and phosphorus (P < .001 for all) were protective factors, and BMD (P = .047) was a risk factor for CR. Multivariable logistic regression showed that N-MID, P1NP, ß-CTX, and phosphorus (odds ratio <1, P < .05 for all) were protective factors for CR. Receiver operating characteristic curves showed these indicators to effectively predict CR occurrence (area under the curve >0.7; P < .001). CONCLUSION: Adolescents with low serum N-MID, P1NP, ß-CTX, and phosphorus levels were associated with a higher risk of CR. We suggest that these indicators can guide clinicians in the early detection and prevention of CR in adolescents.

Nirogacestat suppresses RANKL-Induced osteoclast formation in vitro and attenuates LPS-Induced bone resorption in vivo.

Bone resorption, initiated by osteoclasts (OCs), plays an essential role in bone homeostasis. The abnormalities of bone resorption may induce a series of diseases, including osteoarthritis, osteoporosis and aseptic peri-implant loosening. Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. However, whether it has the therapeutic effect on abnormal bone resorption remains to be evaluated. In this study, we investigated the role of PF in the regulation of receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis in vitro, and the lipopolysaccharide (LPS)-induced bone resorption in vivo. It was found that PF could suppress the formation of osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, inhibit bone resorption and downregulate the mRNA level of osteoclast-specific markers, including calcitonin receptor (CTR), tartrate resistant acid phosphatase (TRAP), cathepsin K (CTSK), dendritic cell-specific transmembrane protein (Dc-stamp), Atp6v0d2 (V-ATPase d2) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Furthermore, Notch2 signaling, as well as RANKL-induced AKT signaling was significantly inhibited in BMMs. Consistent with in vitro observation, we found that PF greatly ameliorated LPS-induced bone resorption. Taken together, our study demonstrated that PF has a great potential to be used in management of osteolytic diseases.