###### Abstract  
This study examined the effects of high-impact weight-bearing exercise on bone mineral density (BMD) and bone metabolic markers in middle-aged premenopausal women. Forty middle-aged premenopausal women were initially enrolled, but thirty-one participants (40.34 \(\pm\) 3.69 years) completed in the study. The subjects were randomly divided into two groups including the high-impact weight-bearing exercise group (HWE, n = 14) and control group (CON, n = 17). The HWE group participated in the exercise for 50 min a day, three days per week for four months, while the CON group maintained their regular lifestyle. The HWE program included 10 different high-impact weight-bearing exercises such as jumping and running. BMD was measured using DXA (Hologic, QDR 4500W, Marlborough, MA, USA). The bone metabolic markers including serum 25-(OH) D, intact parathyroid hormone (PTH), osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor xB ligand (RANKL), osteoclast (OC), C-terminal telopeptide of type 1 collagen (CTX), and calcium were analyzed. The results showed that the BMDs of femur, lumbar, and forearm did not significantly change during the intervention period in both the HWE and CON groups. A significant decrease in bone formation markers such as OC (\(F\) = 10.514, \(p\) = 0.003, \(\eta_{\text{p}}\)\({}^{2}\) = 0.266) and an increase in bone resorption marker including CTX (\(F\) = 8.768, \(p\) = 0.006, \(\eta_{\text{p}}\)\({}^{2}\) = 0.232) were found only in the CON group, while these values did not change in the HWE group. There was a significant increase in serum 25-(OH) D (\(F\) = 4.451, \(p\) = 0.044, \(\eta_{\text{p}}\)\({}^{2}\) = 0.133) in the HWE group. Our findings suggest that four months of HWE is not sufficient to improve BMD and bone metabolic markers, but this impact exercise program may prevent the age-associated changes in bone turnover markers in middle-aged premenopausal women. high-impact weight-bearing exercise; bone mineral density; bone metabolic markers; serum 25-(OH) D; middle-aged premenopausal women +
Footnote †: journal: Applied Sciences  
mortality rate of 10 to 20% than their counterparts, and osteoporosis has a much higher prevalence rate in women over 45 years of age than other diseases including breast cancer, diabetes mellitus, myocardial infarction [8; 9]. Furthermore, the previous study suggested that the incidence of hip fracture would increase by 310% in men and 240% in women by 2050 due to the growth of the aging population and vulnerability to hip fracture with age [10]. Due to these clinical prescriptions, the diagnosis, consequences, monitoring of treatment, and therapy for osteoporosis are of crucial importance [11]. Analyzing bone turnover markers, an index of bone metabolism, are novel tools that detect bone remodeling dynamics including bone formation and resorption [12]. Bone remodeling is regulated by the activation of osteoclasts and osteoblasts and these biomarkers reflect the current status of bone turnover rate [11]. Bone turnover rate can be examined by analyzing bone formation markers such as bone-specific alkaline phosphatase, procollagen type 1 N propeptide, and osteocalcin (OC) and bone resorption markers including the N-terminal telopeptide of type 1 collagen and C-terminal telopeptide of type 1 collagen (CTX) [13]. It is also actively regulated by various factors such as osteopontin (OPN), osteoprotegerin (OPG), receptor activator of nuclear factor \(\kappa\)B ligand (RANKL), parathyroid hormone (PTH), and vitamin D involved in the bone formation process [14; 15; 16]. RANKL is produced in osteoblasts and stromal cells and is the critical factor for the activation of mature osteoclasts and differentiation of monocyte-macrophage osteoclasts, which are precursors to multinucleated osteoclasts [10]. In contrast, OPG, one of the primary regulators of osteoclast-mediated bone resorption, is a factor observed in bone tissue [16].