Aim. To assess the levels of BGP and BAP and correlate them with the rate of bone remodelling. BMD was measured using the DXA technique with the assessment of T score.
Results. In the group I: BGP were 20.12±0.87ng/mL (p<0.03), those of BAP 13.76±0.6μg/mL (p<0.001) and sT spine were -3.63±0.65DS (p<0.001). In the group II: BGP were 15.12±1.55ng/mL (p<0.05), those of BAP 11.88±0.38μg/mL (p<0.001) and sT spine were -3.78±0.36DS (p<0.001). The control group presented: BGP of 16.22±1.62ng/mL, those of BAP of 8.68±0.44μg/mL and sT spine of -1.78±0.11DS.
Conclusion. Bone resorption begins gradually to outrun a new bone formation rhythm associated with low BMD.
Osteoporosis is characterized by low BMD (bone mineral density) and microarchitectural deterioration of bone tissue, leading to increased bone fragility. Osteocalcin or bone Gla protein (BGP) is a noncollagenous protein found in the bone tissue. Serum osteocalcin is considered as a specific marker of osteoblastic function, as its levels correlated with bone formation. Bone alkaline phosphatase (BAP) is frequently used to monitor bone formation rates in osteoporosis. Bone formation markers are direct or indirect products of active osteoblasts, reflecting different aspects of bone formation. One of our first hypotheses was to try to find out if the correlation of serum levels of BGP and BAP with BMD will make us determine the exact rate of bone remodeling, as we guess to be a relation between them. (spine and/or femoral T-scores) in postmenopausal osteoporosis, as compared to a control group (postmenopausal women without osteoporosis). We tried to find relationships between bone mineral density and the levels of studied bone markers in patients, as compared to control group.
Serum levels of BGP and BAP were measured by a sandwich ELISA (enzymelinked immunosorbent assay) technique using:
– The ELISA ACTIVE® OSTEOCALCIN in human serum (from Diagnostic Systems Laboratories, Inc. USA); the assay performance was characterized by a lower detection limit of 0.05-2.5ng/mL, conversion factors: ng/mLx0.17=nmol/mL, and the mean of precision (intra-assay of variation was 3- 5% respectively);
– The ELISA OCTEIATM Ostase® BAP in human serum (from IDS Inc. USA); the assay performance was characterized by a lower detection limit of 0.7μg/L, conversions factor: 1 U/L=0.0369 μg/L, and the mean of precision (intraassay of variation was 2.6-6.5%, respectively). The mean age of subjects was significantly increased between group I and controls, respectively group II and controls (p<0.03 versus p<0.01) II). The BMD decreased predominantly at the level of spine (Ltotal). In group I the s BGP were significantly increased at 136.37% (p<0.002). In group II, the same levels were significantly decreased at 93.22% (p<0.003), comparatively to the controls. The serum levels of BAP ranged from 12.55 to 14.65μg/mL for group I and from 11.34 to 12.57 μg/mL for group II. For the controls, the serum levels of BAP ranged from 8.19 to 9.56 μg/mL. In postmenopausal women with osteoporosis, the serum levels of BAP were significantly increased. Group I presented increased mean values of 158.75% (p<0.002) and group II showed mean values of 148.38% (p<0.003). The group II showed also a strong positive correlation between the decrease of s BGP (r=0.665) and low BMD, as a result of low bone formation. Also, in the group II we detected a positive correlation between the increased serum levels of BAP and the low BMD. In the control group it was observed a positive correlation between BMD and serum levels of BGP (r=0.753) and BAP (r=0.711). Bone remodeling involves the removal of bone by osteoclasts, followed by the formation of bone matrix through osteoblasts, subsequently mineralized. The remodeling cycle consists of three consecutive phases: resorption, reversal, and formation. Osteocalcin, one of the very few bone-specific molecules elaborated by osteoblasts and incorporated into the organic matrix of bone, is a widely used marker for bone formation. In postmenopausal osteoporosis, BGP levels are increased. In periodontal disease, there is an increased turnover of alveolar bone, secondary to a dominant bone resorption. The increased bone resorption due to estrogenic deprivation and accelerated loss of bone in the first decade after menopause seem to be the main pathogenic factors in women. Bullon et al. conclude that low serum osteocalcin concentration is associated with a significantly higher percentage of decrease in probing depth and clinical attachment level after periodontal treatment in postmenopausal women. Bone Gla protein represents a marker of bone formation. In postmenopausal osteoporosis, the rhythm of bone formation is decreased, being significantly correlated with low BMD. In this study, the levels of circulating osteocalcin correlated with bone mineralization are also influenced by age. The mineral homeostatic mechanisms in the skeleton are controlled by calcium-regulating hormones: parathyroid hormone (PTH), calcitonin (CT), 1,25(OH)2-vitamin D3 (D3), involved in the activity of bone-resorpting cells (osteoclasts) and estrogens, which regulate the activity of osteoblasts. The osteoblasts also compose the matrix upon which calcium and phosphate can precipitate. Calcium and phosphate ions stimulate the bone Gla protein secretion from osteoblasts and have an important role in the bone antiresorpting activity. The bone levels of these ions decrease and may induce localized bone demineralization (focal bone decalcification process) encouraging osteoporosis bone microfractures/fractures appearance. BAP is a magnesium-dependent enzyme released by osteoblasts, involved in bone mineralization. It is known that magnesium is an essential cofactor for enzymes involved in synthesis of bone matrix. Also it plays a particularly important role in the regulation of bone deposition and resorption. Odabasi et al. demonstrated that BAP and magnesium play a role in bone remodelling, and osteoporotic lesions have been associated with magnesium deficiency. The high serum levels of BAP demonstrate osteoblastic activation, which will increase significantly bone remodeling (group I and II); with a rate of resorption exceeding the osteoblastic synthesis. The bone remodeling unbalance from postmenopausal osteoporosis induces the decrease of bone formation and the increase of bone resorption. In postmenopause, the loss of gonadal functions and aging are the two most important factors contributing to the development of this condition. Bone tissue (both mineral and matrix) is diminished, presumably because osteoclastic resorption exceeds osteoblastic deposition. In this article we have shown BGP and BAP serum levels correlations with BMD in postmenopausal osteoporosis, but there are also other markers of bone remodeling which can give the same good correlation with BMD. Specifically, postmenopausal bone loss occurs primarily in trabecular bone, whereas aging-associated bone loss occurs primarily in cortical bone. In this study, analyzing the obtained results, we observed a significantly lower BMD, predominantly at lumbar spines. The low BMD is related with a decreased function of estrogenic receptors (ERα and ERβ) expressed by osteoblasts. In conclusion, the serum levels of BAP are significantly higher in postmenopausal osteoporosis versus postmenopausal women without osteoporosis, attesting osteoblastic activation. The serum levels of BGP in postmenopausal osteoporosis were increased, suggesting that osteoblastic activity is increased, and the decrease may be induced by stimulation of osteoblastic apoptosis, secondary to estrogenic deprivation. The increased rate of bone resorption, determines in these conditions a negative bone balance and osteoporosis acceleration.
Cite This Work
To export a reference to this article please select a referencing style below: