PROGNOSTIC ROLE OF MATRIX METALLOPROTEINASE-9 IN PATIENTS WITH CHRONIC HEART FAILURE ASSOCIATED WITH OSTEOPOROSIS AND TYPE 2 DIABETES MELLITUS

CHYNGYSHPAEV D.SH, SHILOV S.N, BEREZIKOVA E.N, MOLOKOV A.V, UZAKOV O.ZH, EFREMOV A.V.

Key words:

MATRIX METALLOPROTEINASES, HEART FAILURE, OSTEOPOROSIS, BONE MINERAL DENSITY, PROGNOSIS, BISPHOSPHONATES

Abstract:

Goal: To investigate the prognostic role of matrix metalloproteinase-9 (MMP-9) in association with bisphosphonate therapy as a biomarker for osteoporosis progression and the risk of bone fractures in patients with chronic heart failure (CHF) associated with type 2 diabetes mellitus (T2DM).

Materials and methods: A 24-month prospective clinically controlled study was conducted on 75 women (mean age 57.4±5.4 years) with chronic heart failure (CHF) associated with type 2 diabetes and osteoporosis. The clinical course of osteoporosis was analyzed, taking into account the level of MMP-9 in the blood plasma in three tertiles. In addition to the basic therapy for CHF, 28 patients were prescribed the drug alendronate for osteoporosis treatment. Tertile 1-1 (n=25) included patients with a minimum MMP-9 level of less than 20.4 ng/ml; Tertile 2 (n=25) consisted of women with MMP-9 levels of 20.4-23.9 ng/ml; Tertile 3 (n=25) included patients with MMP-9 levels exceeding 23.9 ng/ml. The content of serum MMP-9 was determined using enzyme immunoassay. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Outcomes: After 24 months, the combined endpoint incidence was assessed, including a decrease in bone mineral density (BMD) according to dual-energy X-ray absorptiometry and/or the development of osteoporotic fractures. The frequency of adverse events gradually increased from the 1st Tertile through the 3rd Tertile (p = 0.001). Among women with comorbid pathology having a median MMP-9 level above 22.2 ng/ml and BMD (according to T-criterion) less than -2.5, the highest frequency (61.1%) of adverse osteoporotic events was identified. In the group of women receiving alendronate, there was a significant (p=0.029) decrease in MMP-9 levels after 24 months of observation. Conversely, in the group of patients receiving only basic therapy for chronic heart failure (CHF), no significant changes in MMP-9 were detected (p =0.321) Conclusion: Elevated levels of MMP-9 are linked to the progression of bone mineral density (BMD) loss and an increased risk of osteoporotic fractures. Studying the MMP-9 levels in the blood of women with chronic heart failure (CHF) and T2 DM provides valuable insights into assessing the risk of developing osteoporotic fractures. Furthermore, the treatment of osteoporosis with alendronate is associated with a reduction in MMP-9 levels.