This study found that the serum sclerostin level in patients with non-functioning pituitary adenoma was significantly higher than in the healthy population. In parallel with this, we found that all non-functioning pituitary adenoma bone parameters were significantly lower than those of the control group. That indicates that non-functioning pituitary adenomas increase serum sclerostin by an unclear mechanism and that sclerostin damages bone by known mechanisms (osteoblast inhibition and osteoclast activation).
Sclerostin discovery with diseases called sclerosteosis and van Buchem, which are characterized by excessive bone formation. In the studies conducted in the following years, it was determined that there was an inactivating mutation in the SOST gene in these diseases, resulting in the absence or deficiency of sclerostin. Sclerostin prevents osteoblast activation. At the same time, increased sclerostin decreases osteoprotegerin, leaving RANKL exposed and increasing osteoclastogenesis. Thus, sclerostin damages the bone by decreasing osteoblastogenesis and increasing osteoclastogenesis (4, 5).
The Wnt pathway is essential in bone remodeling. Bone formation increases in Wnt activation. Bone destruction is reduced. Sclerostin is an endogenous natural inhibitor of the Wnt pathway. Therefore, a sclerostin antagonist has been developed for the treatment of osteoporosis. This molecule is romosozumab, a human monoclonal antibody developed against sclerostin. Romosozumab increases bone formation and decreases bone resorption (6).
Serum sclerostin level decreases with vitamin D replacement (7).
Although the bone mineral density is normal in acromegalic patients, bone fractures occur. In a study, serum sclerostin levels were found to be high in active acromegalic patients (8).
Intermittent or continuous infusion of parathormone and serum sclerostin levels decrease primary hyperparathyroidism (9).
The incidence of partial pituitary insufficiency in non-functioning pituitary adenomas is present in almost half of the patients. The most common growth hormone deficiency is observed, followed by gonadotropin deficiency (10, 11). The hormonal profile of all patients included in our study was evaluated as usual. However, we may not have detected mild insufficiency. That may indicate that growth hormone deficiency and gonadotropin deficiency adversely affect the bone parameters of our patients.
Kuo et al. They. Investigated bone markers and BMD in 89 patients with chronic kidney disease-related mineral and bone disease who received peritoneal dialysis. That study found positive correlations with serum sclerostin level, male gender, high weight, tall height, serum 25(OH)vitamin D level, creatinine, hemoglobin, glucose level, vertebral BMD, vertebra T, and Z scores, and negatively correlated with PTH level (12). In addition, the positive correlation between serum sclerostin level height and BMD in this study; It seems to contradict the work of Cosman et al. In the study of Cosman et al.; In women with post-menopausal osteoporosis who received anti-sclerostin treatment (Romosozumab), a low rate of vertebral fracture was found, and it was reported that the BMD-reducing effect of sclerostin was supported by this (13). In our study, in patients with NFHA, serum sclerostin level was higher than in the healthy control group, and our bone parameters were found to be lower in the NFHA group than in the control group. This supported the effect of serum sclerostin levels on reducing BMD, but in our study, Kuo et al. As determined, No correlation was found between serum sclerostin levels and BMD, T, and Z scores. When we evaluate the factors affecting this, Kua et al. Grouped the serum sclerostin level above and below the median value. They correlated the bone parameters with the serum sclerostin level above the median value. While performing the correlation test in our study, such a limit value was not considered, and such a grouping was not made.
Czajkowska et al. 31 perimenopausal, 54 post-menopausal patients; investigated estrone, testosterone, andrestenedione, DHEA-S, osteocalcin, β-CTX (cross-linked C telopeptide of type 1 collagen), 25(OH)vit D and serum sclerostin level. Estrone and total testosterone were measured high in the perimenopausal group, and plasma osteocalcin and β-CTX levels, which are markers of bone resorption, were found to be higher in the post-menopausal group. However, they found serum sclerostin levels and 25-(OH) Vit D levels similar in both groups. They found no correlation between serum sclerostin levels and all investigated parameters (14). In our study, although the serum sclerostin level was measured higher and the bone parameters were lower than the control group, There was no correlation between serum sclerostin level and bone parameters. In our study, individuals with normal serum hormone and mineral parameters were evaluated; however, bone resorption markers such as plasma osteocalcin and β-CTX level were not examined. Therefore, according to our study results, we think the relationship between serum sclerostin level and bone formation-resorption in NFHA patients is more complicated. Studies with more comprehensive parameters, perhaps serum cytokine levels, and more extensive case series will explain the different results between clinics on this subject.
The strengths of our study are that it is the first study in the literature to show the relationship between non-functioning pituitary adenoma and sclerostin, the patient population has normal pituitary hormones, the patient population has normal calcium, phosphorus, parathormone, 25-OH vitamin D levels, and the tertiary endocrine center patient population data.
The main limitation of our study is the small number of patients due to the rarity of non-functioning pituitary adenomas.
In conclusion, increased serum sclerostin levels in non-functioning pituitary adenomas negatively affect bone parameters. This study will lead to further studies on the etiopathogenesis of increased sclerostin in non-functioning pituitary adenomas.