Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Abstract

Background: Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures.

Aims and methods: To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured.

Results: CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death.

Conclusion: SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets.

Keywords: 25(OH)D; PTH; bone turnover; cardiovascular disease; hip fracture; mineral metabolism; secondary hyperparathyroidism.

Figure 1

Odds ratios for presence of cardiovascular disease in older patients with hip fracture according to serum parathyroid hormone and urinary deoxypyridinoline levels. Notes: High levels were defined as exceeding the upper limits of normal range: >6.8 pmol/L for serum PTH and >7.5 nmol/μmol for urinary DPD/Cr. Adjustment was made for age, sex, smoking status, alcohol consumption, dementia, hip-fracture type, eGFR < 60 mL/minute/1.73 m², 25(OH)D < 50 nmol/L and albumin < 33 g/L. The odds ratios compared to the reference group (both PTH and DPD/Cr in the normal range) are shown. Abbreviations: PTH, parathyroid hormone; DPD/Cr, deoxypyridinoline corrected by urinary creatinine; 25(OH)D, 25-hydroxyvitamin D; eGFR, estimated glomerular filtration rate.

Figure 2

Diagram showing significant independent relationships (as documented by multiple regression analyses) between cardiovascular disease and parameters of mineral-bone metabolism, age and sex and short-term outcomes. Notes: Minus signs imply a negative (inverse) relationship; myocardial injury defined as cardiac troponin I rise (>0.06 μmol/L). Abbreviations: CVD, cardiovascular disease; SHPT, secondary hyperparathyroidism (PTH > 6.8 pmol/l); high DPD/Cr, deoxypyridinoline corrected by urinary creatinine excretion > 7.5 nmol/μmol; CKD ≥ 3, chronic kidney disease stage 3 or higher (eGFR < 60 mL/minute/1.73 m²); LOS, length of hospital stay; PTH, parathyroid hormone; eGFR, estimated glomerular filtration rate.