Objectives: Chronic kidney disease is associated with mineral and bone disorders, including abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D metabolism, as well as bone diseases like renal osteodystrophy. Although renal transplant can improve some bone mineral disorders, osteoporosis and altered bone metabolism remain important issues due to factors like corticosteroid use and persistent hyperparathyroidism. Bone biopsies are the gold standard for diagnosing bone disorders but are invasive, leading to the exploration of noninvasive methods such as bone turnover markers and bone mineral density measurements. In this study, we aimed to investigate whether there is a relationship between bone turnover markers and bone mineral densities measured by dual-energy X-ray absorptiometry.
Materials and Methods: This study evaluated 121 renal transplant patients categorized as normal, with osteopenia, or with osteoporosis based on dual-energy X-ray absorptiometry measurements. Biochemical markers (parathyroid hormone, alkaline phosphatase, calcium, phosphorus, vitamin D, beta-CrossLaps, and osteocalcin) were analyzed for their relationship with bone mineral density.
Results: Osteoporosis was more common in women (34.09%) than in men (9.09%), likely because of postmenopausal hormonal changes. No significant correlation between bone mineral density and bone turnover markers was observed, and none of the biochemical markers demonstrated strong predictive value for osteoporosis.
Conclusions: Findings suggested that bone mineral density alone is insufficient to fully evaluate bone health, as bone turnover can vary significantly among individuals. A more comprehensive assessment combining bone mineral density, bone turnover markers, and clinical findings is necessary for a better understanding of bone health in renal transplant patients. However, the study’s limitations, including a relatively small sample size, single-point measurements, and lack of follow-up, underscore the need for larger, longitudinal studies. Such studies are essential to better understand bone turnover dynamics and to develop optimized screening and treatment strategies for this patient population.

Key words : Beta-Cross-Laps, Kidney transplantation, Osteocalcin

Introduction
Chronic kidney disease (CKD) is associated with bone mineral disorders, which are significant complications contributing to morbidity and mortality.¹ Components of CKD-mineral and bone disorder include abnormalities in calcium, phosphorus, parathyroid hormone (PTH), and vitamin D metabolism (laboratory abnormalities); bone disease (related to bone turnover, mineralization, volume, and linear growth); and vascular or soft tissue calcification. The bone abnormalities associated with CKD-mineral and bone disorder are termed renal osteodystrophy, which, based on bone biopsy, is classified into high-turnover bone disease, low-turnover bone disease, and mixed bone disease. Other bone abnormalities, such as dialysis-related amyloidosis and osteoporosis, are not included within the definition of renal osteodystrophy.² Although bone mineral disorders in CKD patients may improve to some extent after renal transplantation, renal osteodystrophy remains common in renal transplant recipients. In addition, osteoporosis continues to be a frequent and clinically important problem in this population as a result of posttransplant factors such as corticosteroid use, persistent hyperparathyroidism, and altered bone metabolism. Therefore, evaluating bone health in renal transplant patients remains crucial for prevention of long-term skeletal complications.^3,4 Because of uncertainty surrounding the specific type of bone mineral disorder in these patients, concerns have been raised about the blanket use of antiresorptive agents. With high prevalence of adynamic bone disease, performing a bone biopsy before the initiation of antiresorptive therapy is advisable. This strategy enables the precise ability to assess a patient’s bone turnover status and customize the treatment plan. Indeed, the gold standard test for diagnosis of bone mineral disorders is bone biopsy; however, because of its invasive nature, noninvasive diagnostic methods are being explored. During bone formation and resorption, levels of certain substances in blood and urine, known as bone turnover markers (BTMs), fluctuate. Bone turnover markers include bone formation markers secreted by osteoblasts and bone resorption markers secreted by osteoclasts.⁵ Beta CrossLaps (beta-CTx, used to measure beta-C-terminal telopeptide) is used as a bone resorption marker, whereas alkaline phosphatase (ALP), osteocalcin, and type 1 N-terminal propeptide of collagen are used as bone formation markers.⁶ The International Osteoporosis Foundation recommends serum type 1 N-terminal propeptide of collagen as a marker of bone formation and beta-CTx as a marker of bone resorption.⁷ Clinical studies on biochemical markers reflecting bone turnover have shown an increase in these markers as bone density decreases, supporting the use of these markers as potential indicators for predicting osteoporosis.^5,7,8 Brown and colleagues found that BTMs were not useful in diagnosis of osteoporosis in postmenopausal women but could be a promising tool for monitoring the treatment of osteoporosis.⁵ Elevated levels of BTMs have been shown to be associated with increased bone remodeling and indicate a deterioration in bone quality.⁸ Bone mineral density (BMD) indicates the presence of osteoporosis but does not directly provide information about bone turnover, whereas BTMs reflect bone turnover but are not directly associated with bone mass or fracture risk. Dolgos and colleagues highlighted that dual-energy X-ray absorptiometry (DEXA) measurements can be used to assess bone loss after kidney transplant but emphasized the importance of combining these results with biochemical markers for a more comprehensive evaluation.⁹ In this context, combining BMD and BTMs may provide a practical alternative for evaluation of bone health in patients where bone biopsy is not performed. In this study, we thus aimed to evaluate the relationship between BMD and BTMs (beta-CTx, osteocalcin, 25- hydroxyvitamin D, ALP, calcium, phosphorus, PTH) in renal transplant patients and investigate the predictive value of noninvasive methods to assess bone health.

Materials and Methods
We reviewed patient and digital records of renal transplant patients who presented to the nephrology outpatient clinics of Istanbul Medeniyet University Hospital from August 2023 to November 2023 were reviewed. Demographic characteristics (age, sex), years since renal transplant, and current treatments were obtained from patient files. For each patient, we obtained corrected calcium, phosphorus, ALP, PTH, 25- hydroxyvitamin D, beta-CTx, and osteocalcin results. We also recorded femur and L1-L4 T or Z scores and BMD measurements from radiological data for each patient. Included patients were grouped according to BMD measurements and compared based on laboratory results. The study was conducted in accordance with the principles of the Declaration of Helsinki. Approval was obtained from the Clinical Research Ethics Committee of Istanbul Medeniyet University (approval date: December 13, 2023, decision No: 2023/0877). Written informed consent was obtained from all participants before inclusion in the study.

Inclusion and exclusion criteria
We included renal transplant recipients aged 18 years or older. We excluded patients with pregnancy, glomerular filtration rate <15 mL/min/1.73 m², patients with missing medical records, patients with lack of BMD measurement within the past year, and patients with absence of corrected calcium, phosphorus, ALP, PTH, 25-hydroxyvitamin D, beta-CTx, or osteocalcin data.

Definitions
Patients were osteoporotic if BMD T/Z scores were -2.5 SD or lower, indicating values 2.5 SD below the mean for a young-adult reference population.¹⁰ Patients were osteopenic is BMD T/Z scores were between -1 and -2.5 SD, that is, 1 to 2.5 SD below the young-adult reference mean.¹⁰ Patients were nonosteoporotic/nonosteopenic if BMD T/Z scores were above -1 SD or within 1 SD of the young-adult reference mean.¹⁰ T scores were used for postmenopausal women and men aged >50 years. Z scores were used for premenopausal women and men aged <50 years. Vitamin D deficiency was described as 25-hydroxyvitamin D level of <10 ng/mL. Vitamin D insufficiency was described as 25-hydroxyvitamin D level between 10 and 20 ng/mL.

Statistical analyses
We presented descriptive statistics for continuous variables as mean ± SD or median (interquartile range [IQR]) depending on the data distribution and categorical variables as count and percentage. We assessed the normality of numerical data with the Kolmogorov-Smirnov test. Because data did not follow a normal distribution, non-parametric tests were used for comparisons. We used the Kruskal-Wallis test to compare more than 2 independent groups; in cases where significant differences were detected, we used the post hoc Dunn test to determine the source of the difference. We used the χ2 test to evaluate relationships between categorical variables. We assessed the diagnostic performance of BTMs (corrected calcium, phosphorus, ALP, PTH, 25-hydroxyvitamin D, beta-CTx, and osteocalcin) in predicting osteoporosis by using receiver operating characteristic (ROC) analysis, and the area under the curve (AUC) was reported. P ≤ .⁰⁵ indicated statistical significance. We conducted all analysis with SPSS version 23.0 (SPSS Inc).

Results
Between August 2023 and November 2023, 141 kidney transplant patients followed at the nephrology clinic were initially reviewed. However, 6 patients without BMD measurements within the past year and 14 patients with missing laboratory data (corrected calcium, phosphorus, ALP, PTH, beta-CTx, and osteocalcin) were excluded. Consequently, 121 eligible patients were included in the final analysis. Table 1 lists the basic clinical characteristics of included patients. Patients were categorized based on DEXA results into normal BMD (n = 38, 31.4%), osteopenic (n = 61, 50.4%), and osteoporotic (n = 22, 18.2%) groups. Osteoporosis was significantly more prevalent in women (34.1%) than in men (9.1%) (P < .⁰⁵). Osteopenia rates were similar between men and women (44.1% in men, 45.4% in women) (P > .⁰⁵). The mean femoral neck BMD was significantly higher in men (905.18 ± 144.94 g/cm²) compared with women (790.29 ± 125.44 g/cm²) (P < .⁰⁰¹). Similarly, L1-L4 BMD was 1190.36 ± 169.16 g/cm² in men and 1049.79 ± 175.34 g/cm² in women. The difference was significant (P < .⁰⁰¹). The mean corrected calcium levels were 9.45 ± 0.71 mg/dL in patients with osteoporosis, 9.36 ± 0.50 mg/dL in patients with osteopenia, and 9.26 ± 0.60 mg/dL in those with normal BMD. No significant differences were observed between these groups (P > .⁰⁵). Among patients who were receiving vitamin D therapy, calcium levels were 9.54 ± 0.74 mg/dL in those on active vitamin D, 9.36 ± 0.56 mg/dL in those receiving standard vitamin D supplementation, and 9.19 ± 0.55 mg/dL in those not receiving vitamin D therapy. No significant association was found between calcium levels and vitamin D therapy across groups (P > .⁰⁵). In addition, no correlation was observed between calcium levels, vitamin D therapy, and BMD (P > .⁰⁵). The mean phosphorus levels were 3.47 ± 0.75 mg/dL in patients with osteoporosis, 3.36 ± 0.64 mg/dL in patients with osteopenia, and 3.41 ± 0.54 mg/dL in those with normal BMD. No significant differences were observed between these groups (P > .⁰⁵). No significant correlation was found between phosphorus levels and BMD (P > .⁰⁵). Mean ALP levels were 89.95 ± 56.34 IU/L in patients with osteoporosis, 73.24 ± 21.69 IU/L in patients with osteopenia, and 84.23 ± 23.43 IU/L in patients with normal BMD (P > .⁰⁵). A positive correlation was observed between ALP and BMD in men (P = .⁰¹), but no significant association was found in women. No significant correlation was found between ALP values and BMD when all patients were evaluated (P > .⁰⁵). The mean PTH levels were 104.09 ± 102.36 ng/L in patients with osteoporosis, 72.49 ± 39.69 ng/L in patients with osteopenia, and 66.80 ± 40.76 ng/L in those with normal BMD. No significant differences were observed between these groups (P > 0.05). In addition, no significant correlation was found between PTH levels and femoral or L1-L4 BMD (P > .⁰⁵). The mean vitamin D levels were 39.29 ± 23.14 µg/L in patients with osteoporosis, 31.21 ± 13.67 µg/L in patients with osteopenia, and 24.74 ± 9.25 µg/L in those with normal BMD. Most patients were receiving vitamin D therapy, including 21 of 22 patients in the osteoporotic group (95.5%) and 54 of 61 patients in the osteopenic group (88.5%). A significant negative correlation was observed between vitamin D levels and L1-L4 BMD (r = -0.24, P = .⁰⁰⁷) as well as femoral neck BMD (r = -0.25, P = .⁰⁰⁴). The mean beta-CTx, a bone resorption marker, was 0.48 ± 0.24 ng/mL in men and 0.67 ± 0.46 ng/mL in women, with a significant difference between men and women (P < .⁰⁵). However, when analyzed separately, no significant correlation was found between beta-CTx and BMD in either group (P > .⁰⁵). Among BMD categories, mean beta-CTx levels were 0.66 ± 0.50 ng/mL in osteoporotic patients, 0.51 ± 0.28 ng/mL in patients with osteopenia, and 0.54 ± 0.34 ng/mL in those with normal BMD. No significant differences were observed between these groups (P > .⁰⁵). When men and women were analyzed separately for osteoporosis presence, beta-CTx levels did not significantly differ between groups (P > .⁰⁵). In addition, no significant correlation was found between beta-CTx and femoral BMD (P = .¹⁴) or L1-L4 BMD (P = .¹⁶). Similarly, beta-CTx levels were not significantly associated with vitamin D levels (P > .⁰⁵). The mean osteocalcin, a bone formation marker, was 24.20 ± 11.93 ng/mL in men and 42.53 ± 52.97 ng/mL in women, with no significant difference (P > .⁰⁵). Osteocalcin levels were also not correlated with BMD in either group (P > .⁰⁵). Among BMD categories, the mean osteocalcin levels were 50.58 ± 67.33 ng/mL in the osteoporotic group, 26.25 ± 21.30 ng/mL in the osteopenic group, and 26.86 ± 14.66 ng/mL in the normal BMD group. No significant differences were observed between these groups (P > .⁰⁵) (Table 2). When men and women were analyzed separately based on osteoporosis status, osteocalcin levels did not significantly differ between groups (P > .⁰⁵). However, a weak but significant negative correlation was found between osteocalcin and femoral BMD (r = -0.18, P = .⁰⁴⁹), whereas no correlation was observed with L1-L4 BMD (P = 0.68) or vitamin D levels (P = .⁴⁴). Of the 22 osteoporotic patients, 19 were receiving only vitamin D therapy, whereas 3 were receiving both bisphosphonate and vitamin D therapy. The average beta-CTx level in patients not receiving bisphosphonates was 0.71 ng/mL, osteocalcin level was 53.6 ng/mL, PTH level was 370 ng/L, and ALP level was 93 IU/L. In contrast, the average beta-CTx level in patients receiving bisphosphonates was 0.36 ng/mL, osteocalcin level was 31.2 ng/mL, PTH level was 409 ng/L, and ALP level was 69 IU/L. In ROC analysis to evaluate the predictability of osteoporosis by corrected calcium, phosphorus, ALP, PTH, 25-hydroxyvitamin D, beta-CTx, and osteocalcin levels, AUC was calculated as 0.56 for corrected calcium, 0.53 for phosphorus, 0.55 for ALP, 0.62 for 25-hydroxyvitamin D, 0.58 for beta-CTx, and 0.60 for osteocalcin. Thus, results indicated that laboratory parameters such as calcium, phosphorus, ALP, PTH, 25-hydroxyvitamin D, beta-CTx, and osteocalcin could not predict osteoporosis (Figure 1). The predictability of osteoporosis by corrected calcium, phosphorus, ALP, PTH, 25-hydroxyvitamin D, beta-CTx, and osteocalcin levels was evaluated separately for women and men using ROC analysis. The AUC was 0.50 in women and 0.49 in men for corrected calcium, 0.66 in women and 0.34 in men for phosphorus, 0.52 in women and 0.47 in men for ALP, 0.38 in women and 0.61 in men for 25-hydroxyvitamin D, 0.61 in women and 0.38 in men for beta-CTx, and 0.57 in women and 0.42 in men for osteocalcin. Thus, when patients were examined separately as women and men, laboratory parameters could not predict osteoporosis.

Discussion
Challenges in screening and diagnosing bone loss persist after renal transplant. Renal transplant patients are exposed to numerous factors such as hyperparathyroidism, steroid use, vitamin D supplementation, and altered kidney function that influence bone metabolism, making it difficult to observe a uniform pattern in bone turnover. Bone biopsies are performed in a few specialized centers, and the use of biochemical markers like ALP remains limited. Ongoing experimental studies are investigating whether newer BTMs may be considered as alternatives to bone biopsy.¹¹ Bone mineral density indicates the presence of osteoporosis but does not directly provide information about bone turnover. Patients with osteoporosis may exhibit heterogeneous bone turnover states Although some patients may have low bone turnover (adynamic bone disease), others may experience high bone turnover (high-turnover osteoporosis). Consequently, the combined interpretation of BMD and BTMs is crucial. This approach not only reflects the static measure of BMD but also provides insight into the dynamic status of bone remodeling, which is especially important in planning patient treatment. In line with findings of Caglar and Adeera, our study demonstrated that BMD measurements in the femur and/or lumbar regions were higher in males than in females, which may be attributed to the fact that many female patients, with a mean age of 52 years, were in the postmenopausal period.¹² Similarly, we found that the rate of osteoporosis was significantly higher in women (34.1%) than in men (9.1%), whereas osteopenia rates were comparable between sexes. This finding aligns with previous studies indicating that postmenopausal hormonal changes contribute to accelerated bone loss in women.¹³ In a study from Isiktaş and colleagues, lumbar BMD loss was more prominent during the first 6 months after transplant, possibly due to the increased sensitivity of trabecular bone in the lumbar region from posttransplant steroid use.¹⁴ Conversely, cortical bone in the femoral neck is more sensitive to hyperparathyroidism, leading to greater BMD loss in follow-up after 6 months. Our study similarly found that the mean lumbar BMD was higher than femoral neck BMD. The lower BMD in the femur may be attributed to the mean PTH level of 76.45 ng/L and an average transplant duration of 16.9 years among our patients. Some studies have suggested a potential inverse relationship between phosphorus levels and BMD, although this association remains inconsistent.^15,16 In our study, no significant correlation was found between phosphorus levels and BMD. This discrepancy may be attributed to individual variations in bone remodeling or other confounding factors such as medication use, renal function, and dietary intake. Moreover, our ROC analysis revealed that phosphorus did not have sufficient diagnostic power for predicting osteoporosis, further suggesting that, although phosphorus plays a role in bone metabolism, it may not serve as a reliable independent marker for bone health assessment in long-term transplant recipients. Similarly, calcium homeostasis plays a crucial role in posttransplant bone health. In patients with CKD, a reduction in calcium levels triggers an increase in PTH, leading to secondary BMD loss.^17,18 Although a decrease in PTH levels is expected within the first 6 months after kidney transplant, 30% to 60% of patients experience persistent hyperparathyroidism after transplant. Elevated PTH levels contribute to increased serum calcium and decreased BMD.¹⁹ In our study, although patients with osteoporosis had slightly higher average calcium levels, the difference was not significant versus other groups. This finding may be explained by the complex interplay between PTH, calcium regulation, and vitamin D supplementation in the posttransplant setting and may be attributed to elevated PTH levels and the fact that 95% of patients were using vitamin D supplements, which would enhance and further regulate calcium absorption, potentially masking differences in serum calcium levels between osteoporotic, osteopenic, and normal BMD groups. In our examination of the effects of PTH levels on BMD, no significant relationship was found. In the literature, PTH is reported to have negative effects on BMD, particularly in cortical bone regions (eg, femoral neck).²⁰ However, the lack of a significant relationship in our study may be attributed to individual differences within the patient group, variability in PTH levels, or limitations in BMD measurements. In addition, the widespread use of vitamin D supplements among patients may have masked the effects of PTH on bone. The relationship between vitamin D and BMD, on the other hand, showed a negative trend, contrary to expectations. This finding may be because a large proportion of patients who were osteoporotic and osteopenic (95% and 88.5%, respectively) were receiving vitamin D supplementation. Although the increase in vitamin D levels was due to supplementation, the low BMD in these patients suggested that the bone loss caused by prior vitamin D deficiency could not be fully compensated. Similarly, Battaglia and colleagues found no association between vitamin D levels and BMD, and the relationship between BMD and vitamin D remains debated in the literature.²¹ In the study from Karataş and colleagues, low vitamin D was identified as a risk factor for osteoporosis in renal transplant patients; our findings showed an increase in vitamin D levels as BMD decreased, likely due to the widespread use of vitamin D supplements in our patients.²² Furthermore, the absence of serial BMD measurements made it difficult to evaluate the long-term effects of vitamin D supplementation. The inability to clearly establish the relationships between PTH, vitamin D, and BMD may be due to differences within the patient group, the treatments used, and measurement limitations. Although ALP is a marker of bone turnover, total ALP can originate from various tissues, including bone, liver, intestine, and placenta, When bone density decreases, osteoblasts are activated, producing unmineralized bone-like tissue, which releases bone-specific ALP, thereby increasing serum ALP levels.²³ It is difficult to draw definitive conclusions about bone turnover without measuring bone-specific ALP. Although total ALP can indicate osteoblast function, its specificity is low, leading to its frequent use as a routine screening test.²⁴ Shu and colleagues²⁵ found a negative correlation between total ALP and lumbar BMD, whereas a cross-sectional study in Pakistan found no relationship between total ALP and BMD.²⁶ In our study, we found a significant positive correlation between ALP and BMD in men, whereas no such association was observed in women. This positive correlation in men may be attributed to the regulatory effects of testosterone, which enhances osteoblastic activity and promotes bone formation, thereby strengthening the link between ALP levels and BMD. In contrast, postmenopausal hormonal changes and other factors affecting bone turnover in women might explain the lack of a significant correlation between ALP and BMD. Moreover, ROC analysis indicated that ALP did not have predictive value for BMD. Therefore, for a more specific evaluation of bone turnover, measurement of bone-specific ALP levels is necessary. Bone turnover markers are blood and urine biomarkers used to assess bone remodeling, which consists of continuous cycles of bone resorption by osteoclasts and bone formation by osteoblasts. Osteoporosis disrupts this balance, leading to increased bone fragility. Among bone resorption markers, beta-CTx (C-terminal telopeptide of type 1 collagen) is widely recognized as an indicator of osteoclastic activity and overall bone resorption.²⁷ In Zhao and colleagues, postmenopausal women with low BMD exhibited higher mean beta-CTx levels; however, no significant association between beta-CTx levels and BMD was established.²⁸ Similarly, in our study, beta-CTx levels tended to increase as BMD decreased, but this trend did not reach statistical significance. In addition, no direct correlation was found between BMD and beta-CTx, suggesting that, although beta-CTx reflects bone turnover activity, this marker may not serve as a strong predictor of BMD. Interestingly, our study showed that beta-CTx levels were significantly higher in women than in men (P < .⁰⁵), which could be attributed to postmenopausal hormonal changes that accelerate bone resorption. However, when we compared osteoporotic and nonosteoporotic groups, no significant differences in beta-CTx levels were observed. This may be the result of variability in individual bone turnover rates, the influence of confounding factors such as vitamin D status, renal function, and medication use, or the potential limitations of a single-point measurement in capturing dynamic bone remodeling processes. These findings highlight the complexity of using beta-CTx as a biomarker in osteoporosis assessment and reinforce the importance of integrating multiple diagnostic tools, including clinical risk factors and imaging modalities like DEXA, for a comprehensive evaluation of bone health. Among bone formation markers, osteocalcin, a noncollagen protein secreted by osteoblasts, was shown to be higher in those with low BMD in the study from Xu and colleagues.²⁹ Studies from Ito and colleagues in hemodialysis patients and Vergnaud and colleagues in elderly French women reported a negative correlation between femoral neck BMD and osteocalcin levels.^30,31 In our study, osteocalcin levels were found to be significantly elevated in osteoporotic patients and showed a weak negative correlation with femoral BMD. This finding may reflect increased bone turnover in the pathophysiology of osteoporosis. However, ROC analysis results indicated that osteocalcin does not have sufficient diagnostic power for osteoporosis. Therefore, although osteocalcin levels provide insight into bone turnover, its use as a diagnostic marker is limited. Thus, osteocalcin should be interpreted in conjunction with other biochemical markers and clinical assessments. Furthermore, our ROC analysis indicated that biochemical markers such as PTH, ALP, calcium, phosphorus, vitamin D, beta-CTx, and osteocalcin did not demonstrate sufficient diagnostic power for predicting osteoporosis. The highest AUC was found for 25-hydroxyvitamin D (0.62), followed by osteocalcin (0.60) and beta-CTx (0.58), none of which were strong predictors of osteoporosis. These findings suggest that, while calcium and phosphorus contribute to bone metabolism, they are not reliable markers for osteoporosis diagnosis. Instead, they should be interpreted alongside clinical assessments and imaging modalities such as DEXA to provide a comprehensive evaluation of bone health in transplant recipients. In renal transplant patients, a comprehensive evaluation of bone health should incorporate BMD assessments, BTMs, and clinical findings to guide treatment decisions. Although our study observed a trend toward higher beta-CTx and PTH levels in osteoporotic patients, these differences did not reach statistical significance, and only osteocalcin showed a weak correlation with BMD, particularly in cases of femoral neck osteoporosis. This underscores that relying solely on BMD measurements may not capture the full spectrum of bone remodeling abnormalities. In our study, 22 osteoporotic patients were evaluated, of whom 19 were receiving only vitamin D therapy, whereas 3 patients were receiving both bisphosphonate and vitamin D therapy. The average beta-CTx level in patients not receiving bisphosphonates was 0.71 ng/mL, osteocalcin level was 53.6 ng/mL, PTH level was 370 ng/L, and ALP level was 93 IU/L. In contrast, the average beta-CTx level in patients receiving bisphosphonates was 0.36 ng/mL, osteocalcin level was 31.2 ng/mL, PTH level was 409 ng/L, and ALP level was 69 IU/L. Although BTMs were lower in patients who were receiving bisphosphonates compared with those not receiving them, the differences were not significant. The lack of statistical significance may be explained by several factors. First, the duration of bisphosphonate use was unknown, which could have influenced the observed BTM levels. Second, baseline ALP levels before treatment initiation were not available, making it difficult to assess the degree of change in bone turnover. Lastly, the small sample size, with only 3 patients receiving bisphosphonate therapy, likely limited the statistical power of the analysis. These limitations highlight the need for larger, longitudinal studies with detailed treatment histories to better evaluate the effects of bisphosphonates on BTMs in renal transplant patients.

Limitations
The limited sample size, single-point measurement, and lack of posttreatment follow-up in our study represent important limitations. These factors may have influenced the results and obscured the potential predictive value of BTMs for BMD. Individualized evaluation and serial assessments are necessary to capture the dynamic nature of bone remodeling and to guide the management of medical treatments, particularly in the context of renal transplant patients who may be at risk for adynamic bone disease.

Conclusions
In renal transplant patients, the use of a comprehensive approach that integrates BMD measurements, BTMs, and clinical findings is needed. Although BMD remains a widely used indicator, BMD alone cannot fully capture the complexity of bone health, as bone turnover can be heterogeneous within this patient population. The assessment of BTMs, along with clinical risk factors, is crucial to understanding the underlying causes of osteoporosis and ensuring tailored treatments. Given the limitations and findings of our study, further research with larger, prospectively designed cohorts and serial measurements is needed to better inform treatment strategies and improve clinical outcomes in this patient group. This approach will enhance our understanding of bone turnover dynamics and optimize therapeutic interventions in renal transplant recipients.