FGF23 Beyond the Kidney: A New Bone Mass Regulator in the General Population

Abstract

Clinical studies investigating the relationship between fibroblast growth factor 23 (FGF23) and bone mass are controversial, especially in the healthy renal population. Our study is one of the forefronts investigating the relationship between FGF23 and bone mass parameters in the general population, according to age, sex, menopausal, and nutritional status. Cross-sectional study enrolling 123 volunteers between 20–80 years of age without primary osteoporosis under treatment nor secondary osteoporosis, where bone mass (bone mineral density-BMD, bone mineral content-BMC; assessed by Dual X-Ray Absorptiometry-DXA), body composition (DXA evaluation), and also the serum levels of FGF23, parathormone (PTH), 25(OH)D, bone resorption marker C-terminal telopeptide of type I collagen (CTx) and leptin were determined. FGF23 was negatively and independently associated with BMD and/or BMC in all groups. FGF23 contributed to up to 10% (p <0.05) of femoral neck BMD variance in postmenopausal women, but was not an accurate discriminator of normal versus low bone mass (AUC=0.622±0.076). FGF23 did not correlate with 25(OH)D, CTx, body weight, body composition parameters or leptin. FGF23 was independently associated with PTH in premenopausal women and men only. FGF23 was negatively associated with bone mass parameters in both sexes, but was not a fine discriminator between normal bone mass and osteopenia/osteoporosis. The mechanism through which FGF23 acts upon the bone seems independent of the nutritional status, requiring further investigation.

Glucocorticoid induced bone disorders in children: Research progress in treatment mechanisms

“…Fibroblast growth factor 23 (FGF23) is a hormone synthesized by bone cells that regulates the 'bone-kidney' axis and calcium phosphate metabolism (40)(41)(42). FGF23 reduces serum phosphate levels by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption (43), while also reducing plasma calcitriol levels by down-regulating the expression of the renal 1-a hydroxylase and up-regulates 24-hydroxylase (44).…”

Fibroblast Growth Factor 23 and Osteoporosis: Evidence from Bench to Bedside

“…[ N/A Serum FGF23 level was independently associated with decreasing BMD in the femoral neck in post-menopausal women. [4] a adjusted by multivariate analysis, b univariate correlation, C C-terminal fragment FGF23 (kRU/L) ELISA, E intact FGF23 two site monoclonal ELISA, I intact FGF23 polyclonal ELISA; Values are expressed as mean ± SD and median (IQR), ↑↑: very significant increased, ↑: significant increased, ↔: no significant difference, ↓: significant decrease, ↓↓: very significant decrease (within study comparison); Abbreviations: BALP, bone alkaline phosphatase; BMD, bone mineral density; BV/TV, bone volume/trabecular volume; CTX-1, serum c-telopeptide of type 1 collagen; FN, femoral neck, FT, Femoral trochanter; N/A, data not available; OC, serum osteocalcin; P1NP, serum propeptide of type 1 procollagen; PF, proximal femur, LS: lumbar spine; ref., reference (comparison group by univariate analysis), TH, total hip; Tb.N, trabecular number; Tb.Th, trabecular thickness; TRAP5b, serum tartrate-resistant acid phosphatase 5b.…”

“…Another study in men with osteoporosis also showed that femoral neck BMD was not significantly changed in different FGF23 quartiles [ 28 ]. In contrast, the studies in post-menopausal women found that FGF23 had a strong negative correlation with BMD [ 1 ] and a significant association with femoral BMD after adjusting for PTH, 25(OH)D, and leptin [ 4 ]. Furthermore, another cross-sectional study in osteoporosis patients, in which the majority are women, demonstrated a weak independent association between high FGF23 and deceased trabecular bone microarchitecture but not cortical bone [ 3 ].…”

“…Furthermore, the three aforementioned studies discovered an independent association between elevated FGF23 and the incidence of fragility fractures in both moderate CKD and ESRD patients [ 28 , 34 , 35 ]. Even though FGF23 levels had an independent negative relationship with BMD in postmenopausal women [ 1 , 4 ], it was not an effective discriminator between osteopenia/osteoporosis and normal bone mass [ 4 ]. In addition, utilizing the FGF23 level for osteoporosis prediction in hemodialysis patients resulted in poor discrimination [ 44 ].…”

“…Structural integrity of the bone is maintained through intricate and interrelated activities of bone-forming osteoblasts, bone-resorbing osteoclasts, physicochemical conditions that modulate local matrix mineralization, and systemic mineral homeostasis. Over the last ten years, the association between fibroblast growth factor 23 (FGF23) and osteoporosis has been studied [ 1 , 2 , 3 , 4 ]. FGF23 is a bone-derived endocrine factor that regulates phosphate and vitamin D homeostasis via the fibroblast growth factor receptors (FGFRs)/αKlotho complex.…”