Classification of bone turnover and calcium metabolism markers based on the molecular subtypes of osteogenesis imperfecta

Aylin Gunay; Canbaz Aylin Tugba; Ilknur Kurt; Elif Kelestemur; Ahmet Kahveci; Tosun Busra Gurpinar; Didem Helvacioglu; Abali Zehra Yavas; Belma Haliloglu; Tulay Guran; Abdullah Bereket; Serap Turan

doi:10.1530/endoabs.110.P207

JOINT2234

Introduction and Aim: Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility, with molecular subtypes influencing its severity and clinical presentation. This study aims to investigate how bone turnover and calcium metabolism markers vary across these subtypes.

Method: The medical records of 125 OI patients were retrospectively reviewed. Patients without genetic results, and those without pre-treatment bone turnover markers (BTMs) were excluded. A total of 83 patients (43 females) were included. Patients were classified into five molecular subgroups: Group-1 (collagen synthesis, n = 53), Group-2 (collagen modification, n = 9), Group-3 (collagen folding, n = 10), Group-4 (bone mineralization, n = 6), and Group-5 (osteoblast development, n = 5). Pre-treatment measurements of calcium metabolism markers (serum calcium, phosphorus, alkaline phosphatase [ALP], parathyroid hormone [PTH], and urinary calcium/creatinine [uCa/Cr]) and BTMs (osteocalcin, C-terminal telopeptide [CTX] and deoxypyridinoline [DPD]) were analyzed, and each parameter’s age- and sex-adjusted standard deviation score (SDS) was calculated for intergroup comparisons. DPD and CTX could not be evaluated in all patients.

Results: One-way ANOVA revealed significant differences in osteocalcin levels among five groups, with post-hoc analysis identifying the difference between group 1 and 2 as the primary contributor. Phosphorus levels also showed a significant difference, driven by differences between group 1 and 2 (P = 0. 02) and group 1 and 3 (P = 0. 03). No significant differences were observed between groups for serum calcium, ALP, PTH, and uCa/Cr. DPD levels differed between groups 2 and 3. CTX levels differed between Groups 1 and 3 (Table).

Table 1: OI molecular subtypes and comparision of BTMs and calcium metabolism markers
GROUP	1 COL1A1 COL1A2 BMP1 SPARC	2 CRTAP P3H1	3 FKBP10 PLOD2	4 IFITM5 SERPINF1	5 WNT1 MBTPS1 SP7 LRP5	p
OC-SDS	1,82±2,86^†	-1,14±0,58^†	0,12±1,48	-0,78±2,59	0,57±2,61	0,005^†
Ca-SDS	0,04±0,05	0,04±0,04	0,02±0,054	-0,01 (-0,05-0,02)	0,01±0,03	0,27^§
PO4-SDS	-0,09±1,49^†	-1,68±1,87^†	-0,51±1,08	-1,93±0,78^†	-0,30±1,07	0,0048^†
ALP-SDS	0,58 (-0,18-1,36)	3,11±2,78	1,33 (-0,09-4,27)	2,10±2,03	2,33±2,32	0,081^§
PTH-SDS	-1,24(-1,84- -0,34)	-1,64(-2,11- -0,09)	-1,59±0,85	-1,32±0,46	-1,93±0,88	0,243^§
uCa/Cr-SDS	0,23 (-1,15-1,53)	0,79±1,23	0,15 (-1,77-11,2)	-0,63±1,19	2,45±5,01	0,60^§
DPD-SDS	0,01(-0,04-0.16)	0,44±0,42^§	-0,03±0,14^§	*	*	0,0432^§
CTX-SDS	-0,11±0,06	*	-0,002±0,15	*	*	0,0084^¥

Conclusion: High osteocalcin and phosphorus indicate active bone formation and mineralization, with low CTX suggesting lesser collagen degradation in group 1. Low osteocalcin and high DPD in Group 2 suggest impaired formation and excessive collagen degradation. Group 3 had low DPD but high CTX, reflecting ongoing osteoclast activity and unstable collagen resorption due to impaired cross-links. These findings offer insights into OI pathophysiology and support subtype-specific therapeutic approaches.

Keywords: osteogenesis, bone turnover markers, calcium metabolism

Endocrine Abstracts

P207