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Association of aberrant mineral metabolic markers with fracture risk in chronic kidney disease: a comprehensive meta-analysis

BMC Nephrology volume 26, Article number: 68 (2025) Cite this article

Abstract

Background

This meta-analysis aims to investigate the impact of abnormalities in mineral metabolic markers, including serum phosphate and calcium, intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF23) on the risk of fractures in patients with chronic kidney disease (CKD).

Methods

A systematic search was conducted across MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials. The outcomes were association of mineral metabolic markers with the risk of fractures in patients with chronic kidney disease. Pooled risk estimates and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models.

Results

Thirty-two studies were included in the meta-analysis. High and low levels of serum phosphate in hemodialysis (HD) patients were both associated with an increased risk of fractures (RR = 1.08, 95% CI 1.02–1.15, P = 0.013; RR = 1.13, 95% CI 1.02–1.25, P = 0.022, respectively). Similarly, abnormal levels of iPTH in CKD patients, both high and low, were associated with increased fracture risk (RR = 1.25, 95% CI 1.20–1.31, P < 0.001; RR = 1.41, 95% CI 1.10–1.82, P = 0.007, respectively). Elevated FGF23 levels were also linked to an increased risk of fractures (RR = 1.32, 95% CI 1.06–1.66, P = 0.015). While a higher level of calcium exhibited a trend towards reduced fracture incidence without statistical significance (RR = 0.90, 95% CI 0.77–1.05, P = 0.181), lower calcium levels tended to increase fracture risk without statistical significance (RR = 1.11, 95% CI 0.99–1.24, P = 0.087). Notably, subjects treated with calcium and phosphorus modulating drugs demonstrated a statistically significant reduction in fractures among CKD patients undergoing dialysis (phosphate binders, RR = 0.79, 95% CI 0.70–0.89; cinacalcet, RR = 0.74, 95% CI 0.59–0.93; vitamin D analogues, RR = 0.82, 95% CI 0.74–0.92, respectively).

Conclusion

This meta-analysis underscores the association between abnormal mineral metabolic markers, including high serum phosphate, iPTH, and FGF23, and an increased risk of fractures in CKD patients. Notably, both elevated and decreased levels of phosphate and iPTH contribute to fracture risk. The efficacy of active vitamin D, phosphorus binders, and cinacalcet in preventing fractures was observed in HD patients but not in the non-dialysis CKD population.

Trial registration

PROSPERO CRD42023493951.

Peer Review reports

Introduction

Chronic kidney disease (CKD) stands as a prominent health concern, frequently precipitating heightened cardiovascular and cerebrovascular complications [1]. Early in the trajectory of CKD, disruptions in mineral metabolism emerge, exerting a pivotal influence on the acceleration of metabolic irregularities [2]. Clinical investigations have underscored a discernible association between bone and mineral metabolism aberrations and an augmented susceptibility to fractures [3]. The Dialysis Outcomes and Practice Patterns Study (DOPPS) II, encompassing 12 participating countries, reported an incidence of 8.9 per 1000 patient years for new hip fractures and 25.6 per 1000 for any new fracture among hemodialysis (HD) patients [4].

The primary culprits implicated in elevated fracture risk in CKD include bone loss, secondary hyperparathyroidism (SHPT), deficiency in 1,25-dihydroxydroxy vitamin D, chronic acidosis, and heparin exposure [5]. Numerous clinical studies and reviews have proposed that CKD-mineral and bone disorder (CKD-MBD), marked by conditions such as hyperphosphatemia, compromised activation of vitamin D, SHPT, and elevated fibroblast growth factor 23 (FGF23), significantly contribute to the heightened fracture risk [4, 6,7,8]. Nevertheless, the precise fracture risk in CKD and its correlation with surrogate markers of CKD-MBD remain elusive. Inconsistencies in findings regarding the association between mineral bone metabolic markers and fracture risk in the CKD population have been documented [4, 9,10,11,12].

Thus, the primary objective of this meta-analysis is to affirm the relationship between mineral bone metabolic markers and the risk of fractures in CKD patients. Furthermore, our investigation seeks to elucidate the potential efficacy of phosphorus binders, active vitamin D, and the calcium-sensing receptor agonist-cinacalcet in mitigating fracture risk within both dialysis and non-dialysis CKD populations.

Methods

We adhered to a standardized protocol in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study is prospectively registered with PROSPERO under the registration number CRD42023493951, ensuring transparency and methodological rigor in our research process.

Search strategy and study selection

We implemented a comprehensive search strategy to identify relevant literature from multiple databases, including MEDLINE (PubMed, January 1, 1966, to January 31, 2024), Web of Science, EMBASE (January 1, 1966, to January 31, 2024), ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials. The search utilized specific keywords such as “serum phosphate,” “parathyroid hormone,” “fibroblast growth factor 23,” “calcium,” “phosphate binders,” “cinacalcet,” “vitamin D analogues,” in conjunction with “chronic kidney disease” and “fracture.” Detailed search strategies for each database are outlined in Table S1. Additionally, manual searches of references cited in identified original studies and pertinent review articles were conducted and assessed for inclusion. The stepwise procedures are elucidated in Figure S1.

Inclusion and exclusion criteria

Studies that met the following criteria were included in our meta-analysis: 1) Studies involving patients with CKD. 2) Inclusion of randomized controlled trials (RCTs), non-randomized trials, and prospective or observational studies. 3) Evaluation of fractures associated with high or low levels of serum phosphate, parathyroid hormone, fibroblast growth factor 23 (FGF23), or calcium, as compared to a control group with normal levels of these parameters in CKD patients. 4) Assessment of fractures related to the use of phosphate binders, cinacalcet, or vitamin D analogues, in comparison with a control group receiving placebo or no treatment in CKD patients.

Studies were excluded if they met any of the following criteria: 1) Studies where the outcomes of fractures were not reported. 2) Different publications analyzing the same population or duplicates. 3) Studies involving population post-kidney transplantation.

Data collection

Three researchers (Y Liu, ZX Zhang, CS Fu) performed the search and reviewed the results. Data were independently extracted by the three researchers Y Liu, ZX Zhang, CS Fu) who reviewed all the study characteristics (i.e., first author’s surname, year of publication, study design, sample, follow-up, and outcomes). Any disagreement in data extraction was resolved through a discussion among these researchers in consultation with the other authors (XH Yang, HM Jin and ZB Ye).

Assessment of heterogeneity

Heterogeneity assessment employed Cochran’s Q and I2 statistics. A study was deemed heterogeneous if the P-value was less than 0.1 (Cochran’s Q). Studies with I2 values below 50% were categorized as non-heterogeneous, warranting the use of a fixed-effects model in their analysis. Conversely, studies with I2 values exceeding 50% were considered heterogeneous and were subjected to analysis using a random-effects model.

Risk of bias assessment

The assessment of the quality of included non-randomized controlled trials (non-RCTs) was conducted using the ‘Risk of Bias in Non-randomized Studies of Interventions’ (ROBINS-I) tool. The studies were evaluated for the risk of bias in seven domains and subsequently ranked as low, moderate, serious, or critical risk of bias.

Statistical analyses

Data analysis was performed utilizing STATA version 17.0 (StataCorp, TX, USA). Risk ratios (RRs) for fractures were computed, and all pooled estimates are presented with corresponding 95% confidence intervals (CIs). Additionally, a sensitivity analysis was conducted, involving the extraction of each study to assess its impact on the overall estimate. To investigate the presence of publication bias, Egger’s test was employed. A significance threshold of P < 0.05 was set for all statistical analyses.

Results

Study flow and study characteristics

The selection process for inclusion is delineated in Figure S1 and Table S1. A comprehensive screening process identified 196 potentially relevant citations, which were subsequently evaluated, leading to the retrieval of 32 articles for in-depth examination [4, 9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]. The pertinent characteristics of the 32 included studies are summarized in Table 1. The meticulous risk assessment of these studies utilizing the ROBINS-I tool is presented in detail in Table S2.

Table 1 The pertinent characteristics of the 32 included studies
Full size table

Effect of serum inorganic phosphate (Pi) on fracture endpoints

Normal phosphate levels are defined as ranging from 1.13 to 1.78 mmol/L. Phosphate levels above 1.78 mmol/L are considered high, while levels below 1.13 mmol/L are classified as low. These thresholds are based on the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The pooled results from nine studies involving CKD patients revealed that high Pi levels posed a heightened risk of fractures compared to the intermediate range (Fig. 1A, RR = 1.08, 95% CI 1.02–1.15, P = 0.013). Similarly, results pooled from five studies involving CKD patients undergoing hemodialysis demonstrated that a low level of Pi increased the risk of fractures when compared to the intermediate range (Fig. 1B, RR = 1.13, 95% CI 1.02–1.25, P = 0.022).

Fig. 1
figure 1

Risk ratios (RRs) for fractures in CKD patients associated with inorganic phosphate (Pi) levels from pooled studies. A Pooled results from studies assessing fractures associated with high Pi. B Pooled results from studies assessing fractures associated with low Pi

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Effect of iPTH levels on fracture endpoints

The thresholds for high and low PTH levels were chosen based on clinical guidelines (K/DOQI). For dialysis patients, maintaining iPTH levels between 150 and 300 pg/mL is the recommended target range. In our meta-analysis, we defined high PTH as greater than 300 pg/mL and low PTH as below 150 pg/mL. In contrast to the intermediate iPTH levels, a comprehensive analysis of pooled results from 11 studies revealed that elevated iPTH levels significantly increased the risk of fractures in patients with dialysis (Fig. 2A, RR = 1.25, 95% CI 1.20–1.31, P < 0.001).

Fig. 2
figure 2

Risk ratios (RRs) for fractures in dialysis patients associated with intact parathyroid hormone (iPTH) levels from pooled studies. A Pooled results from studies assessing fractures associated with high iPTH. B Pooled results from studies assessing fractures associated with low iPTH

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Additionally, findings from 10 studies indicated that lower iPTH levels were associated with an elevated risk of fractures in dialysis patients (Fig. 2B, RR = 1.41, 95% CI 1.10–1.82, P = 0.007, I2 = 71.5). Considering the notable heterogeneity, we categorized the studies by study type, which substantially reduced the heterogeneity (Figure S2, cohort study, I2 = 47.1%; retrospective study, I2 = 0.0%).

Effect of FGF23 levels on fracture endpoints in CKD patients without dialysis

No pertinent literature was found to explore the impact of FGF23 on fracture endpoints in CKD patients undergoing dialysis. Consequently, our focus was directed towards CKD patients without dialysis. This meta-analysis was conducted on six study arms that reported fracture endpoints. The pooled results revealed that elevated FGF23 levels (> 58 pg/ml) were associated with an increased risk of fracture outcomes (RR = 1.32, 95% CI 1.06–1.66, P = 0.015, Fig. 3).

Fig. 3
figure 3

Risk ratios (RRs) for fractures in CKD patients without dialysis associated with fibroblast growth factor-23 (FGF23) levels from pooled studies

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Effect of serum corrected calcium on fracture endpoints in CKD patients on dialysis

In our meta-analysis, we explored the impact of serum calcium on fracture endpoints in CKD patients undergoing dialysis. The K/DOQI guidelines recommend that the target range for serum calcium is 2.1–2.51 mmol/L. Low calcium was defined as levels below 2.1 mmol/L, intermediate calcium as levels between 2.1 and 2.51 mmol/L, and high calcium as levels above 2.51 mmol/L. When compared to the intermediate calcium levels, a higher calcium level appeared to confer a potential benefit in reducing the incidence of fractures, although this trend lacked statistical significance (RR = 0.90, 95% CI 0.77–1.05, P = 0.181; Fig. 4A). Conversely, lower calcium levels exhibited a tendency to increase the risk of fractures, though again without statistical significance (RR = 1.11, 95% CI 0.99–1.24, P = 0.087; Fig. 4B).

Fig. 4
figure 4

Risk ratios (RRs) for fractures in CKD patients with dialysis associated with calcium (Ca) levels from pooled studies. A Pooled results from studies assessing fractures associated with high Ca. B Pooled results from studies assessing fractures associated with low Ca

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Effect of phosphate binders, cinacalcet, and vitamin D analogues on fracture endpoints in CKD patients

As depicted in Fig. 5A, individuals treated with medications addressing abnormal calcium and phosphorus metabolism exhibited statistically significant reductions in fractures among CKD patients undergoing dialysis (phosphate binders, RR = 0.79, 95% CI 0.70–0.89; cinacalcet, RR = 0.74, 95% CI 0.59–0.93; vitamin D analogues, RR = 0.82, 95% CI 0.74–0.92; respectively) compared to control groups. However, in non-dialysis patients, there was a limited number of studies investigating the effects of these drugs on final fracture endpoints. The pooled results from three studies on drugs and fracture endpoints were inconclusive, suggesting that calcium and phosphorus-modulating drugs were not associated with a decreased risk of fracture when compared to control groups in CKD patients not undergoing dialysis (Fig. 5B; phosphate binders, RR = 1.07, 95% CI 0.90–1.27; vitamin D analogues, RR = 0.95, 95% CI 0.66–1.37; respectively).

Fig. 5
figure 5

Risk ratios (RRs) for fractures in CKD patients associated with drug treatments from pooled studies. A Pooled results from studies assessing fractures in CKD patients with dialysis of drug treatments. B Pooled results from studies assessing fractures in CKD patients without dialysis of drug treatments

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Sensitivity analysis and publication bias

The sensitivity analysis indicated that the exclusion of any individual study from the meta-analysis did not alter the overall conclusions (Figure S3). Publication bias was assessed using Egger’s test for studies exceeding 10 in number. Consequently, no publication bias was detected in the pooled studies (high Pi with fracture, P = 0.065; high iPTH with fracture, P = 0.555; calcium and phosphorus-modulating drugs treatment with fracture, P = 0.070; Figure S4).

Discussion

This meta-analysis represents the inaugural attempt to elucidate the association between mineral bone metabolic markers and the risk of fractures in CKD. Our findings indicate that elevated phosphorus, high iPTH, and increased FGF-23, as well as decreased phosphorus and diminished iPTH, are all associated with an elevated risk of fractures in the CKD population.

As has been previously suggested, existing literature proposes that bone loss is a primary contributor to fractures [2, 3, 12]. Experimental CKD studies demonstrate distinct regulatory roles of high serum Pi and iPTH in bone loss and vascular calcification [40]. The Wnt/β-Catenin signaling pathway is crucial for normal bone mineralization, osteoblastic activity, osteocyte function, and overall bone health [41]. In CKD, this pathway is dysregulated, contributing to impaired bone remodeling and fragility. Wnt signaling is involved in osteoblast differentiation and bone matrix production, as well as osteocyte viability and communication, all of which are vital for bone integrity [42, 43]. Recent studies have shown that FGF23 inhibits the Wnt pathway, exacerbating bone loss in CKD [44]. Elevated FGF23 levels in uremic models suppress Wnt signaling, leading to reduced osteoblastic activity and bone formation. Additionally, iPTH enhances FGF23 expression, further inhibiting Wnt signaling, which results in a cycle of bone resorption and mineralization defects [45]. Besides Wnt/β-Catenin, other pathways like RANK/RANKL/OPG also contribute to CKD-related bone disorders [46]. These pathways collectively influence bone fragility in CKD, highlighting the need for targeted therapies to modulate them and improve bone health in this population.

In pre-dialysis CKD patients, an iPTH level below 70 pg/ml was associated with a high risk of low bone mineral density (BMD), and patients with adynamic bone disease (ABD) and osteomalacia (OM) exhibited lower trabecular bone volume. Low turnover bone disease, as manifested by ABD and OM, emerged as a hallmark of bone loss [47]. Bone histomorphometric analysis also indicated an independent correlation between serum FGF23 levels and bone volume parameters in rats with experimentally induced CKD [48].

The mechanism by which hyperphosphatemia induces an elevated risk of fractures is not fully elucidated. Potential mechanisms include the suppression of osteoblastic proliferation through insulin-like growth factor 1 and osteopontin gene expression [49]. Hyperphosphatemia has also been implicated in increasing osteoblast apoptosis and reducing bone formation [50], as well as inhibiting bone resorption through the stimulation of osteoblast-produced osteoprotegerin [51].

Conversely, it is noteworthy that hypophosphatemia is associated with an increased risk of fractures in CKD population. Phosphate plays crucial roles in numerous biological processes, and chronic hypophosphatemia leads to impaired mineralization of the bone matrix, resulting in conditions such as rickets and osteomalacia, as observed in X-Linked Hypophosphatemia (XLH) and FGF23-related hypophosphatemic diseases [52]. Bones from mice with XLH exhibit enlarged osteocyte lacunae, enhanced osteocyte expression of genes related to bone remodeling, and impaired canalicular structure [53]. In vitro studies have demonstrated that hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes [54]. However, research on the relationship between hypophosphatemia and osteoblasts is limited. Future studies on low phosphorus and osteoblasts may provide insights into why low phosphorus increases the risk of fractures.

The efficacy of phosphate binders in reducing the risk of fractures in CKD patients has been a subject of controversy. Phosphate binders encompass calcium-based phosphate binders (CPB) and non-calcium-based phosphate binders (NCPB), including sevelamer and lanthanum. Early studies with small sample sizes in hemodialysis patients suggested that NCPB was associated with lower BMD at the lumbar spine and distal radius compared to CPB [55]. However, another small sample study in incident hemodialysis patients found no significant differences in lumbar and femoral BMD between lanthanum carbonate and calcium carbonate groups [56].

A prospective two-year study in chronic dialysis patients, using dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to measure BMD changes, indicated that vitamin D analogs and phosphate binders did not protect against bone loss [57]. Cinacalcet showed protective effects in univariate analysis but not in multivariable analysis [57]. There are limited trials investigating bone histomorphometric changes through bone biopsy after phosphate binder therapy. A 54-week randomized study with 119 hemodialysis patients comparing the effects of sevelamer hydrochloride and calcium carbonate on bone demonstrated that sevelamer did not result in statistically significant changes in bone turnover or mineralization compared to calcium carbonate. However, sevelamer was associated with increased bone formation and improved trabecular architecture [58]. In a small trial with hemodialysis patients, cinacalcet treatment decreased iPTH and reduced activation frequency, bone formation rate/bone surface, and fibrosis surface/bone surface [59]. Despite the prevalent use of paricalcitol or doxercalciferol in stage 5 CKD patients, there is limited prospective human research on their effects on bone. A six-month prospective trial demonstrated that calcitriol treatment decreased bone turnover, bone resorption and formation, and reduced woven osteoid and fibrosis. It also improved mineralization and parameters of bone architecture in hemodialysis patients [60]. In rats with CKD, calcitriol positively influenced bone microarchitecture, achieving normal trabecular connectivity [61].

Considering that excessive suppression of iPTH may increase fracture risk, iPTH levels should be monitored during treatment with vitamin D analogs and cinacalcet. Maintaining an appropriate balance between therapeutic benefits and potential risks is essential. Future research should focus on determining the optimal therapeutic range for iPTH suppression to ensure that the fracture risk reduction achieved with these therapies is not compromised by overly aggressive suppression of iPTH.

This meta-analysis is subject to several potential limitations. Firstly, the majority of studies included are observational or prospective/retrospective trials, with only two randomized controlled trials (RCTs). A meta-analysis incorporating high-quality RCT data would enhance the persuasiveness of the findings. Secondly, there is notable heterogeneity in the analysis of the association between low iPTH levels and fracture risk (I squared = 71.5, Fig. 2B), likely due to variations in study design (Figure S2). Future RCTs should further investigate and confirm the association of low iPTH with an increased risk of fractures in CKD population. Thirdly, the limited number of papers addressing low phosphate (5 papers), as well as the effects of vitamin D analogues (5 papers) and cinacalcet (4 papers) on fracture risk in the CKD population, underscores the need for more clinical trials to validate the association of low phosphate with the risk of fractures and to further establish the protective effects of vitamin D analogues and cinacalcet on bone.

In summary, our meta-analysis reveals that elevated serum phosphate, iPTH, and FGF23 are associated with an increased risk of fractures, while low phosphate and low iPTH also contribute to an elevated risk of fractures in CKD population. Regarding calcium levels, while higher calcium levels showed a trend towards reducing fracture risk, this finding was not statistically significant. Similarly, lower calcium levels tended to increase fracture risk, but again, this was not statistically significant. To better understand the relationship between these factors and fracture risk, further research is warranted, particularly regarding the impact of calcium levels on fracture risk in CKD patients. Future studies should consider larger sample sizes and longer follow-up periods to validate these trends and explore potential clinical intervention strategies. Given the limited data available on non-dialysis CKD populations, future research should focus on conducting trials specifically targeting this group to better understand the efficacy of treatments such as phosphate binders, cinacalcet, and vitamin D analogs in non-dialysis patients. Addressing this gap will provide valuable insights and guide clinical decision-making in the management of mineral bone disorders in this population.

Data availability

Data associated with the study has not been deposited into a publicly available repository. Data are available from the corresponding author on reasonable request.

References

  1. Swamy S, Noor SM, Mathew RO. Cardiovascular disease in diabetes and chronic kidney disease. J Clin Med. 2023;12(22):6984. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/jcm12226984.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Bellorin-Font E, Rojas E, Martin KJ. Bone disease in chronic kidney disease and kidney transplant. Nutrients. 2022;15(1):167. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/nu15010167.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Kazama JJ. Chronic kidney disease and fragility fracture. Clin Exp Nephrol. 2017;21(Suppl 1):46–52. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s10157-016-1368-3.

    Article  PubMed  CAS  Google Scholar 

  4. Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, et al. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the dialysis outcomes and practice patterns study. Kidney Int. 2006;70(7):1358–66. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/sj.ki.5001754.

    Article  PubMed  CAS  Google Scholar 

  5. Lafage-Proust MH. Bone and chronic kidney disease. Semin Musculoskelet Radiol. 2023;27(4):463–70. https://doiorg.publicaciones.saludcastillayleon.es/10.1055/s-0043-1770353.

    Article  PubMed  Google Scholar 

  6. Haarhaus M, Aaltonen L, Cejka D, Cozzolino M, de Jong RT, D’Haese P, et al. Management of fracture risk in CKD-traditional and novel approaches. Clin Kidney J. 2022;16(3):456–72. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/ckj/sfac230.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Pazianas M, Miller PD. Osteoporosis and Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): back to basics. Am J Kidney Dis. 2021;78(4):582–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1053/j.ajkd.2020.12.024.

    Article  PubMed  CAS  Google Scholar 

  8. Fusaro M, Holden R, Lok C, Iervasi G, Plebani M, Aghi A, et al. Phosphate and bone fracture risk in chronic kidney disease patients. Nephrol Dial Transplant. 2021;36(3):405–12. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/ndt/gfz196.

    Article  PubMed  CAS  Google Scholar 

  9. Stehman-Breen CO, Sherrard DJ, Alem AM, Gillen DL, Heckbert SR, Wong CS, et al. Risk factors for hip fracture among patients with end-stage renal disease. Kidney Int. 2000;58(5):2200–5. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/j.1523-1755.2000.00394.x.

    Article  PubMed  CAS  Google Scholar 

  10. Danese MD, Kim J, Doan QV, Dylan M, Griffiths R, Chertow GM. PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis. Am J Kidney Dis. 2006;47(1):149–56. https://doiorg.publicaciones.saludcastillayleon.es/10.1053/j.ajkd.2005.09.024.

    Article  PubMed  Google Scholar 

  11. Jovanovich A, Bùzková P, Chonchol M, Robbins J, Fink HA, de Boer IH, et al. Fibroblast growth factor 23, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study. J Clin Endocrinol Metab. 2013;98(8):3323–31. https://doiorg.publicaciones.saludcastillayleon.es/10.1210/jc.2013-1152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Atsumi K, Kushida K, Yamazaki K, Shimizu S, Ohmura A, Inoue T. Risk factors for vertebral fractures in renal osteodystrophy. Am J Kidney Dis. 1999;33(2):287–93. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s0272-6386(99)70302-1.

    Article  PubMed  CAS  Google Scholar 

  13. Coco M, Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis. 2000;36(6):1115–21. https://doiorg.publicaciones.saludcastillayleon.es/10.1053/ajkd.2000.19812.

    Article  PubMed  CAS  Google Scholar 

  14. Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int. 2005;68(4):1793–800. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/j.1523-1755.2005.00596.x.

    Article  PubMed  CAS  Google Scholar 

  15. Kanda E, Yoshida M, Sasaki S. Applicability of fibroblast growth factor 23 for evaluation of risk of vertebral fracture and chronic kidney disease-mineral bone disease in elderly chronic kidney disease patients. BMC Nephrol. 2012;13:122. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/1471-2369-13-122.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Lane NE, Parimi N, Corr M, Yao W, Cauley JA, Nielson CM, et al. Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the Osteoporotic Fractures in Men (MrOS) study. J Bone Miner Res. 2013;28(11):2325–32. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jbmr.1985.

    Article  PubMed  CAS  Google Scholar 

  17. Chen YJ, Kung PT, Wang YH, Huang CC, Hsu SC, Tsai WC, et al. Greater risk of hip fracture in hemodialysis than in peritoneal dialysis. Osteoporos Int. 2014;25(5):1513–8. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00198-014-2632-6. Epub 2014 Feb 21.

    Article  PubMed  CAS  Google Scholar 

  18. Isakova T, Cai X, Lee J, Katz R, Cauley JA, Fried LF, et al. Associations of FGF23 with change in bone mineral density and fracture risk in older individuals. J Bone Miner Res. 2016;31(4):742–8. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jbmr.2750. Epub 2015 Dec 23.

    Article  PubMed  CAS  Google Scholar 

  19. Moe SM, Abdalla S, Chertow GM, Parfrey PS, Block GA, Correa-Rotter R, et al. Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE trial. J Am Soc Nephrol. 2015;26(6):1466–75. https://doiorg.publicaciones.saludcastillayleon.es/10.1681/ASN.2014040414.

    Article  PubMed  CAS  Google Scholar 

  20. Fishbane S, Hazzan AD, Jhaveri KD, Ma L, Lacson E Jr. Bone parameters and risk of hip and femur fractures in patients on hemodialysis. Clin J Am Soc Nephrol. 2016;11(6):1063–72. https://doiorg.publicaciones.saludcastillayleon.es/10.2215/CJN.09280915.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Dey V, Farrah TE, Traynor JP, Spalding EM, Robertson SE, Geddes CC. Symptomatic fracture risk in the renal replacement therapy population. Nephrol Dial Transplant. 2017;32(7):1211–6. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/ndt/gfw222.

    Article  PubMed  CAS  Google Scholar 

  22. Evans M, Methven S, Gasparini A, Barany P, Birnie K, MacNeill S, et al. Cinacalcet use and the risk of cardiovascular events, fractures and mortality in chronic kidney disease patients with secondary hyperparathyroidism. Sci Rep. 2018;8(1):2103. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41598-018-20552-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Hutchison A, Whelton A, Thadhani R, Achenbach H, Vergani A, Wu J, et al. Long-term mortality and bone safety in patients with end-stage renal disease receiving lanthanum carbonate. Nephron. 2018;140(4):265–74. https://doiorg.publicaciones.saludcastillayleon.es/10.1159/000492603.

    Article  PubMed  CAS  Google Scholar 

  24. Desbiens LC, Goupil R, Sidibé A, Madore F, Mac-Way F. Fracture status in middle-aged individuals with early CKD: cross-sectional analysis of the CARTaGENE survey. Osteoporos Int. 2019;30(4):787–95. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00198-019-04902-1.

    Article  PubMed  Google Scholar 

  25. Geng S, Kuang Z, Peissig PL, Page D, Maursetter L, Hansen KE. Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease. Osteoporos Int. 2019;30(10):2019–25. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00198-019-05033-3.

    Article  PubMed  CAS  Google Scholar 

  26. Kwon YE, Choi HY, Kim S, Ryu DR, Oh HJ, ESRD Registry Committee of the Korean Society of Nephrology. Fracture risk in chronic kidney disease: a Korean population-based cohort study. Kidney Res Clin Pract. 2019;38(2):220–8. https://doiorg.publicaciones.saludcastillayleon.es/10.23876/j.krcp.18.0099.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wakasugi M, Kazama JJ, Kikuchi K, Yasuda K, Wada A, Hamano T, et al. Hemodialysis product and hip fracture in hemodialysis patients: a nationwide cohort study in Japan. Ther Apher Dial. 2019;23(6):507–17. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/1744-9987.12807.

    Article  PubMed  CAS  Google Scholar 

  28. Jansz TT, Goto NA, van Ballegooijen AJ, Willems HC, Verhaar MC, van Jaarsveld BC. The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone. Osteoporos Int. 2020;31(3):515–24. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00198-019-05187-0.

    Article  PubMed  CAS  Google Scholar 

  29. Matias PJ, Laranjinha I, Azevedo A, Raimundo A, Navarro D, Jorge C, et al. Bone fracture risk factors in prevalent hemodialysis patients. J Bone Miner Metab. 2020;38(2):205–12. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00774-019-01041-9.

    Article  PubMed  CAS  Google Scholar 

  30. Ribeiro AL, Mendes F, Carias E, Rato F, Santos N, Neves PL, et al. FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease. J Diabetes Complications. 2020;34(1):107476. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jdiacomp.2019.107476.

    Article  PubMed  Google Scholar 

  31. Ogata H, Fukagawa M, Hirakata H, Kagimura T, Fukushima M, Akizawa T, et al. Effect of treating hyperphosphatemia with lanthanum carbonate vs calcium carbonate on cardiovascular events in patients with chronic kidney disease undergoing hemodialysis: the LANDMARK randomized clinical trial. JAMA. 2021;325(19):1946–54. https://doiorg.publicaciones.saludcastillayleon.es/10.1001/jama.2021.4807.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Fusaro M, Cozzolino M, Plebani M, Iervasi G, Ketteler M, Gallieni M, et al. Sevelamer use, vitamin k levels, vascular calcifications, and vertebral fractures in hemodialysis patients: results from the VIKI study. J Bone Miner Res. 2021;36(3):500–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jbmr.4214.

    Article  PubMed  CAS  Google Scholar 

  33. Fusaro M, Cianciolo G, Tripepi G, Plebani M, Aghi A, Politi C, et al. Oral calcitriol use, vertebral fractures, and vitamin K in hemodialysis patients: a cross-sectional study. J Bone Miner Res. 2021;36(12):2361–70. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jbmr.4440.

    Article  PubMed  CAS  Google Scholar 

  34. Xie L, Hu X, Li W, Ouyang Z. A retrospective study of end-stage kidney disease patients on maintenance hemodialysis with renal osteodystrophy-associated fragility fractures. BMC Nephrol. 2021;22(1):23. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12882-020-02224-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Yoshida M, Nakashima A, Doi S, Maeda K, Ishiuchi N, Naito T, et al. Lower Geriatric Nutritional Risk Index (GNRI) is associated with higher risk of fractures in patients undergoing hemodialysis. Nutrients. 2021;13(8):2847. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/nu13082847.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Desbiens LC, Sidibé A, Ung RV, Mac-Way F. FGF23-klotho axis and fractures in patients without and with early CKD: a case-cohort analysis of CARTaGENE. J Clin Endocrinol Metab. 2022;107(6):e2502–12. https://doiorg.publicaciones.saludcastillayleon.es/10.1210/clinem/dgac071.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Murashima M, Hamano T, Nishiyama T, Tsuruya K, Ogata S, Kanda E, et al. Performance status modifies the association between vitamin D receptor activator and mortality or fracture: a prospective cohort study on the Japanese Society for Dialysis Therapy (JSDT) renal data registry. J Bone Miner Res. 2022;37(8):1489–99. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jbmr.4621.

    Article  PubMed  CAS  Google Scholar 

  38. Young TK, Toussaint ND, Di Tanna GL, Arnott C, Hockham C, Kang A, et al. Risk factors for fracture in patients with coexisting chronic kidney disease and type 2 diabetes: an observational analysis from the CREDENCE trial. J Diabetes Res. 2022;2022:9998891. https://doiorg.publicaciones.saludcastillayleon.es/10.1155/2022/9998891.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Barrera-Baena P, Rodríguez-García M, Rodríguez-Rubio E, González-Llorente L, Ortiz A, Zoccali C, et al. Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients. Nephrol Dial Transplant. 2023:gfad190. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/ndt/gfad190.

  40. Carrillo-López N, Panizo S, Alonso-Montes C, Martínez-Arias L, Avello N, Sosa P, et al. High-serum phosphate and parathyroid hormone distinctly regulate bone loss and vascular calcification in experimental chronic kidney disease. Nephrol Dial Transplant. 2019;34(6):934–41. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/ndt/gfy287.

    Article  PubMed  CAS  Google Scholar 

  41. Kronenberg HM. Developmental regulation of the growth plate. Nature. 2003;423(6937):332–6. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/nature01657.

    Article  PubMed  CAS  Google Scholar 

  42. Zheng CM, Hsu YH, Wu CC, Lu CL, Liu WC, Zheng JQ, Lin YF, Chiu HW, Chang TJ, Shyu JF, Lu KC. Osteoclast-released Wnt-10b underlies cinacalcet related bone improvement in chronic kidney disease. Int J Mol Sci. 2019;20(11):2800. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/ijms20112800.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Hung KC, Chang JF, Hsu YH, Hsieh CY, Wu MS, Wu MY, Chiu IJ, Syu RS, Wang TM, Wu CC, Hung LY, Zheng CM, Lu KC. Therapeutic effect of calcimimetics on osteoclast-osteoblast crosslink in chronic kidney disease and mineral bone disease. Int J Mol Sci. 2020;21(22):8712. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/ijms21228712.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Carrillo-López N, Panizo S, Alonso-Montes C, Román-García P, Rodríguez I, Martínez-Salgado C, et al. Direct inhibition of osteoblastic Wnt pathway by fibroblast growth factor 23 contributes to bone loss in chronic kidney disease. Kidney Int. 2016;90(1):77–89. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.kint.2016.01.024.

    Article  PubMed  CAS  Google Scholar 

  45. Lavi-Moshayoff V, Wasserman G, Meir T, Silver J, Naveh-Many T. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010;299(4):F882-9. https://doiorg.publicaciones.saludcastillayleon.es/10.1152/ajprenal.00360.2010.

    Article  PubMed  CAS  Google Scholar 

  46. Carrillo-López N, Martínez-Arias L, Fernández-Villabrille S, Ruiz-Torres MP, Dusso A, Cannata-Andía JB, et al. Role of the RANK/RANKL/OPG and Wnt/β-catenin systems in CKD bone and cardiovascular disorders. Calcif Tissue Int. 2021;108(4):439–51. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00223-020-00803-2.

    Article  PubMed  CAS  Google Scholar 

  47. Lobão R, Carvalho AB, Cuppari L, Ventura R, Lazaretti-Castro M, Jorgetti V, et al. High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis. Clin Nephrol. 2004;62(6):432–9. https://doiorg.publicaciones.saludcastillayleon.es/10.5414/cnp62432.

    Article  PubMed  Google Scholar 

  48. Liao HW, Hung PH, Hsiao CY, Liou HH, Lin HS, Huang TH, et al. Relationship between fibroblast growth factor 23 and biochemical and bone histomorphometric alterations in a chronic kidney disease rat model undergoing parathyroidectomy. PLoS ONE. 2015;10(7):e0133278. https://doiorg.publicaciones.saludcastillayleon.es/10.1371/journal.pone.0133278.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Beck GR Jr, Zerler B, Moran E. Phosphate is a specific signal for induction of osteopontin gene expression. Proc Natl Acad Sci U S A. 2000;97(15):8352–7. https://doiorg.publicaciones.saludcastillayleon.es/10.1073/pnas.140021997.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Meleti Z, Shapiro IM, Adams CS. Inorganic phosphate induces apoptosis of osteoblast-like cells in culture. Bone. 2000;27(3):359–66. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s8756-3282(00)00346-x.

    Article  PubMed  CAS  Google Scholar 

  51. Kanatani M, Sugimoto T, Kano J, Kanzawa M, Chihara K. Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity. J Cell Physiol. 2003;196(1):180–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jcp.10270.

    Article  PubMed  CAS  Google Scholar 

  52. Kinoshita Y, Fukumoto S. X-linked hypophosphatemia and FGF23-related hypophosphatemic diseases: prospect for new treatment. Endocr Rev. 2018;39(3):274–91. https://doiorg.publicaciones.saludcastillayleon.es/10.1210/er.2017-00220.

    Article  PubMed  Google Scholar 

  53. Yuan Y, Jagga S, Martins JS, Rana R, Pajevic PD, Liu ES. Impaired 1,25 dihydroxyvitamin D3 action and hypophosphatemia underlie the altered lacuno-canalicular remodeling observed in the Hyp mouse model of XLH. PLoS ONE. 2021;16(5):e0252348. https://doiorg.publicaciones.saludcastillayleon.es/10.1371/journal.pone.0252348.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Sabbagh Y, Carpenter TO, Demay MB. Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci U S A. 2005;102(27):9637–42. https://doiorg.publicaciones.saludcastillayleon.es/10.1073/pnas.0502249102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Udomkarnjananun S, Phannajit J, Takkavatakarn K, Tumkosit M, Kingpetch K, Avihingsanon Y, et al. Effects of phosphate binders on bone biomarkers and bone density in haemodialysis patients. Nephrology (Carlton). 2022;27(5):441–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/nep.14022.

    Article  PubMed  CAS  Google Scholar 

  56. Goto K, Goto S, Fujii H, Watanabe K, Kono K, Nishi S. Effects of lanthanum carbonate on bone markers and bone mineral density in incident hemodialysis patients. J Bone Miner Metab. 2019;37(6):1075–82. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00774-019-01018-8.

    Article  PubMed  CAS  Google Scholar 

  57. Malluche HH, Monier-Faugere MC, Blomquist G, Davenport DL. Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. Osteoporos Int. 2018;29(1):125–34. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00198-017-4228-4. Epub 2017 Oct 9 PMID: 28993865.

    Article  PubMed  CAS  Google Scholar 

  58. Ferreira A, Frazão JM, Monier-Faugere MC, Gil C, Galvao J, Oliveira C, et al. Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients. J Am Soc Nephrol. 2008;19(2):405–12. https://doiorg.publicaciones.saludcastillayleon.es/10.1681/ASN.2006101089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Malluche HH, Monier-Faugere MC, Wang G, Frazã OJM, Charytan C, Coburn JW, et al. An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism. Clin Nephrol. 2008;69(4):269–78. https://doiorg.publicaciones.saludcastillayleon.es/10.5414/cnp69269.

    Article  PubMed  CAS  Google Scholar 

  60. Malluche HH, Goldstein DA, Massry SG. Effects of 6 months therapy with 1,25 (OH)2D3 on bone disease of dialysis patients. Contrib Nephrol. 1980;18:98–104. https://doiorg.publicaciones.saludcastillayleon.es/10.1159/000403277.

    Article  PubMed  CAS  Google Scholar 

  61. Naves Díaz M, Rodríguez Rodríguez A, Fernández Martín JL, Serrano Arias M, Menéndez Rodríguez P, Cannata Andía JB. Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy. Bone. 2007;41(4):614–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.bone.2007.06.026.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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Author notes

  1. Yao Liu, Zhen Xing Zhang and Chen Sheng Fu contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, Huadong Hospital, Fudan University, Shanghai, 200040, China

    Yao Liu, Zhen Xing Zhang, Chen Sheng Fu, Zhi Bin Ye & Xiu Hong Yang

  2. Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, China

    Yao Liu, Zhen Xing Zhang, Chen Sheng Fu, Zhi Bin Ye & Xiu Hong Yang

  3. Department of Nephrology, the People’s Hospital of Wenshan Prefecture, Yunnan Province, China

    Hui Min Jin

  4. Department of Nephrology, Pudong Medical Center, Shanghai Pudong Hospital, Fudan University, 2800 Gong Wei Road, Shanghai, China

    Hui Min Jin

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Contributions

HM Jin and ZB Ye conceived and designed the study. Y Liu, ZX Zhang, CS Fu selected the articles, extracted and analysed the data. XH Yang wrote the first draft of the manuscript. XH Yang, HM Jin and ZB Ye interpreted the data and contributed to the writing of the final version of the manuscript. All authors agreed with the results and conclusions of this Article. Y Liu, ZX Zhang, CS Fu contributed equally to this paper.

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Supplementary Information

Supplementary Material 1: Figure S1. Study selection process.

12882_2025_3992_MOESM2_ESM.pdf

Supplementary Material 2: Figure S2. Pooled results from studies assessing fractures associated with low iPTH by study type.

12882_2025_3992_MOESM3_ESM.zip

Supplementary Material 3: Figure S3. The sensitivity analyses of studies. (A) The sensitivity analyses of studies assessing fractures associated with high Pi. (B) The sensitivity analyses of studies assessing fractures associated with low Pi. (C) The sensitivity analyses of studies assessing fractures associated with high iPTH. (D) The sensitivity analyses of studies assessing fractures associated with low iPTH. (E) The sensitivity analyses of studies assessing fractures associated with fibroblast growth factor-23 (FGF23). (F) The sensitivity analyses of studies assessing fractures associated with high Ca. (G) The sensitivity analyses of studies assessing fractures associated with low Ca. (H) The sensitivity analyses of studies assessing fractures in CKD patients with dialysis of drug treatments. (I) The sensitivity analyses of studies assessing fractures in CKD patients without dialysis of drug treatments.

12882_2025_3992_MOESM4_ESM.zip

Supplementary Material 4: Figure S4. The Egger’s publication bias plot of studies. (A) The Egger’s publication bias plot of studies assessing fractures associated with high Pi. (B) The Egger’s publication bias plot of studies assessing fractures associated with high iPTH. (C) The Egger’s publication bias plot of assessing fractures in CKD patients with dialysis of drug treatments.

Supplementary Material 5.

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Liu, Y., Zhang, Z.X., Fu, C.S. et al. Association of aberrant mineral metabolic markers with fracture risk in chronic kidney disease: a comprehensive meta-analysis. BMC Nephrol 26, 68 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12882-025-03992-w

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BMC Nephrology

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