Matrix Metalloproteinases/Tissue Inhibitors of Metalloproteinases Ratio: A Biomarker of Bone Resorption in Geriatric Osteoporosis?

Abstract

Background: Matrix metalloproteinases (MMPs) play an important role in bone resorption and are regulated by tissue inhibitors of metalloproteinases (TIMPs). We investigated the use of MMP2/TIMP2 and MMP9/TIMP1 ratios as biomarkers of bone resorption in geriatric osteoporosis and evaluated the relationship between osteoporosis and geriatric syndromes.Methods: This analytical cross-sectional study involved 87 patients (41 with osteoporosis) treated at the geriatric outpatient clinic of a university hospital. The demographic characteristics, comprehensive geriatric assessment scores, laboratory findings, and bone mineral density of the patients were recorded. Serum MMP9, TIMP1, MMP2, and TIMP2 levels were analyzed by enzyme-linked immunosorbent assay (ELISA).Results: We enrolled 41 and 46 patients with and without osteoporosis, respectively. The groups showed no significant differences in MMP2/TIMP2 and MMP9/TIMP1 ratios (p=0.569 and p=0125, respectively). While the basic activities of daily life (BADL) scores in the osteoporosis group were higher than those in the group without osteoporosis, the instrumental activities of daily life (IADL) scores were significantly lower (p=0.001 and p=0.007, respectively). No significant differences were observed in Mini-Nutritional Assessment, Mini-Mental State Examination, and Geriatric Depression Scale scores (p=0.598, p=0.898, and p=0.287, respectively). Conclusion: This is the first study to examine the relationship between osteoporosis and several geriatric syndromes, as well as the relationship between osteoporosis and serum MMP, TIMP values, and MMP/TIMP ratios in geriatric patients. Our results showed that osteoporosis causes dependency in both BADLs and IADLs, and that the MMP2/TIMP2 and MMP9/TIMP1 ratios provided no additional benefit in demonstrating bone resorption in geriatric osteoporosis.

Importance of Metalloproteinase Enzyme Group in Selected Skeletal System Diseases

“…Circulating serum MMP-9 showed a trend of increasing levels from patients with a normal BMD, through patients with a reduced BMD, to patients with established osteoporosis [110,112]. Only one study of all available human studies showed no significant differences in MMP-2 and MMP-9 levels in patients with osteopenia and osteoporosis compared to healthy controls among older patients [116]. MMP-13, on the other hand, showed increased serum levels in the osteopenia patient group compared to healthy controls, while the concentrations were equalized relative to the osteoporosis group [13].…”

Serum levels of matrix metalloproteinases 1, 2, and 7, and their tissue inhibitors 1, 2, 3, and 4 in polytraumatized patients: Time trajectories, correlations, and their ability to predict mortality

“…Extensive research has been conducted on the involvement of MMP1, MMP2, MMP7, and the four TIMPs in cancer progression, migration, and metastasis [6,32,44,45]. Moreover, the serum or plasma levels of these proteins have been investigated in a wide range of diseases, including geriatric osteoporosis (MMP2, TIMP1, TIMP2 [46]), musculoskeletal diseases (MMP1, MMP 2, TIMP1 [47]), vasculitis (MMP1 [48]; MMP2, TIMP1, TIMP 2 [49]), coronary artery disease (MMP1, ). Moreover, the balance between MMP and TIMP levels has been shown to be important.…”

“…Moreover, the balance between MMP and TIMP levels has been shown to be important. As a result, studies have been concentrating on the ratios of MMPs to TIMPs [46,[62][63][64][65][66].…”