Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single‐cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast‐musculature cells and endocrine cells. PC development may be stimulated by fibroblast‐endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).

Sclerostin is a secreted inhibitor of Wnt/β-catenin signaling that is mainly produced by osteocytes and is an important regulator of bone remodeling. Some studies have evaluated serum sclerostin levels in metabolic bone diseases, but the results have been contradictory. The profile of serum sclerostin levels in patients with osteogenesis imperfecta (OI), X-linked hypophosphatemia (XLH), and Paget’s disease of bone (PDB) was obtained to determine their association with bone turnover marker. Serum sclerostin levels, biochemical parameters, and the bone turnover marker, β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), were measured in 278 individuals, comprising 71 patients with OI, 51 patients with XLH, 17 patients with PDB, and 139 age- and sex-matched healthy controls. A correlation analysis was performed between sclerostin and β-CTX concentration. The univariate logistic regression analysis was used to analyze factors associated with OI, XLH, and PDB. Patients with PDB (11 male 6 female), aged 44.47 ± 14.75 years; XLH (17 male, 34 female), aged 19.29 ± 15.65 years; and OI (43 male, 28 female), aged   19.57 ± 16.45 years, had higher sclerostin level than age- and sex-matched healthy controls [median(interquartile range): 291.60 (153.42, 357.35) vs. 38.00 (27.06, 68.52) pmol/L, 163.40 (125.10, 238.20) vs. 31.13 (20.37, 45.84) pmol/L, and 130.50 (96.12, 160.80) vs. 119.00 (98.89, 194.80) pmol/L, respectively; P < 0.001 ]. Patients with PDB had the highest level of serum sclerostin, followed by those with XLH and OI ( P < 0.05 ). Sclerostin was positively correlated with β-CTX in OI and XLH ( r = 0.541 and r = 0.661 , respectively; P < 0.001 ). Higher β-CTX and sclerostin levels were associated with a higher risk of OI, XLH, and PBD. Sclerostin may be a biomarker of OI, XLH, and PDB. Whether sclerostin inhibitors can be used in these patients requires further analysis using additional cohorts.