Advances in alveolar bone changes and risks of alveolar surgery in patients with chronic kidney disease

doi:10.3969/j.issn.1674-8115.2026.07.017

Abstract

Abstract:

Chronic kidney disease (CKD) is a major global public health issue that significantly impacts patients′ health and quality of life. Chronic kidney disease-mineral and bone disorder (CKD-MBD), a common complication of CKD, not only leads to systemic bone metabolic abnormalities but also causes local changes such as a decrease in alveolar bone mass. Its pathological mechanisms involve multiple aspects, including calcium-phosphorus metabolism imbalance, uremic toxin damage, inflammation and oxidative stress, nutritional and metabolic disorders, as well as hormonal and growth factor dysregulation. Renal dysfunction leads to hyperphosphatemia, hypocalcemia, and secondary hyperparathyroidism, disrupting the dynamic balance between bone formation and resorption. The accumulation of uremic toxins and inflammatory cytokines induces oxidative stress, thereby suppressing osteoblast differentiation while promoting osteoclast activation. Moreover, metabolic disturbances, including vitamin D deficiency and protein-energy wasting, along with hormonal and growth factor dysregulation, impair alveolar bone homeostasis and exacerbate bone disorders. When patients with CKD undergo alveolar surgeries, such as tooth extraction and dental implant placement, they face risks of bleeding, infection, and poor wound healing. Therefore, targeted perioperative management is necessary, including multidisciplinary collaboration with nephrologists to comprehensively assess renal and coagulation functions, appropriate surgical timing, the use of minimally invasive techniques, and enhanced infection prevention. This article reviews the characteristics, mechanisms, and clinical risks of CKD-related alveolar bone changes, providing reference for related mechanism exploration and oral diagnosis and treatment.

Key words: chronic kidney disease, chronic kidney disease-mineral and bone disorder, oral cavity, alveolar bone, alveolar surgery

CLC Number:

R782.13

Lu Tingwei, Yuan Hao, Liu Yingli, Jiang Lingyong. Advances in alveolar bone changes and risks of alveolar surgery in patients with chronic kidney disease[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(7): 981-989.

Figures/Tables 2

TrendMD

References 61

[1]	GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2020, 395(10225): 709-733.
[2]	Najar M S, Mir M M, Muzamil M. Prevalence of osteoporosis in patients with chronic kidney disease (stages 3-5) in comparison with age- and sex-matched controls: a study from Kashmir Valley Tertiary Care Center[J]. Saudi J Kidney Dis Transpl, 2017, 28(3): 538-544.
[3]	Aggarwal H K, Jain D, Yadav S, et al. Bone mineral density in patients with predialysis chronic kidney disease[J]. Ren Fail, 2013, 35(8): 1105-1111.
[4]	Kanjevac T, Bijelic B, Brajkovic D, et al. Impact of chronic kidney disease mineral and bone disorder on jaw and alveolar bone metabolism: a narrative review[J]. Oral Health Prev Dent, 2018, 16(1): 79-85.
[5]	You M, Tang B, Wang Z J, et al. Radiological manifestations of renal osteodystrophy in the orofacial region: a case report and literature review[J]. Oral Radiol, 2018, 34(3): 262-266.
[6]	Raubenheimer E J, Noffke C E, Hendrik H D. Chronic kidney disease-mineral bone disorder: an update on the pathology and cranial manifestations[J]. J Oral Pathol Med, 2015, 44(4): 239-243.
[7]	Patil S, Sinha N. Pulp stone, haemodialysis, end-stage renal disease, carotid atherosclerosis[J]. J Clin Diagn Res, 2013, 7(6): 1228-1231.
[8]	Imirzalioglu P, Onay E O, Agca E, et al. Dental erosion in chronic renal failure[J]. Clin Oral Investig, 2007, 11(2): 175-180.
[9]	Davidovich E, Schwarz Z, Davidovitch M, et al. Oral findings and periodontal status in children, adolescents and young adults suffering from renal failure[J]. J Clinic Periodontology, 2005, 32(10): 1076-1082.
[10]	Sezer B, Kaya R, Kodaman Dokumacıgil N, et al. Assessment of the oral health status of children with chronic kidney disease[J]. Pediatr Nephrol, 2023, 38(1): 269-277.
[11]	Caldiroli L, Molinari P, D′Alessandro C, et al. Osteosarcopenia in chronic kidney disease: an overlooked syndrome?[J]. J Cachexia Sarcopenia Muscle, 2025, 16(2): e13787.
[12]	Yuan Q J, Wang J W, Peng Z Z, et al. Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)[J]. J Transl Med, 2019, 17(1): 86.
[13]	Tanaka H, Komaba H, Koizumi M, et al. Role of uremic toxins and oxidative stress in the development of chronic kidney disease-mineral and bone disorder[J]. J Ren Nutr, 2012, 22(1): 98-101.
[14]	de Waal D, Heaslip E, Callas P. Medical nutrition therapy for chronic kidney disease improves biomarkers and slows time to dialysis[J]. J Ren Nutr, 2016, 26(1): 1-9.
[15]	Davenport A. Frailty, appendicular lean mass, osteoporosis and osteosarcopenia in peritoneal dialysis patients[J]. J Nephrol, 2022, 35(9): 2333-2340.
[16]	Messier M D, Emde K, Stern L, et al. Radiographic periodontal bone loss in chronic kidney disease[J]. J Periodontol, 2012, 83(5): 602-611.
[17]	Zhao D, Chen X L, Yue L, et al. Assessment of residual alveolar bone volume in hemodialysis patients using CBCT[J]. Clin Oral Investig, 2015, 19(7): 1619-1624.
[18]	Scutellari P N, Orzincolo C, Bedani P L, et al. Radiographic manifestations in teeth and jaws in chronic kidney insufficiency[J]. Radiol Med, 1996, 92(4): 415-420.
[19]	Guimarães L M, Valeriano A T, Rebelo Pontes H A, et al. Manifestations of hyperparathyroidism in the jaws: concepts, mechanisms, and clinical aspects[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2022, 133(5): 547-555.
[20]	Chapple I L C, Hirschfeld J, Cockwell P, et al. Interplay between periodontitis and chronic kidney disease[J]. Nat Rev Nephrol, 2025, 21(4): 226-240.
[21]	Mohamed F F, Amadeu de Oliveira F, Kinoshita Y, et al. Dentoalveolar alterations in an adenine-induced chronic kidney disease mouse model[J]. J Bone Miner Res, 2023, 38(8): 1192-1207.
[22]	Zhao D, Zhang S W, Chen X L, et al. Evaluation of periodontitis and bone loss in patients undergoing hemodialysis[J]. J Periodontol, 2014, 85(11): 1515-1520.
[23]	Sun K, Shen H, Liu Y L, et al. Assessment of alveolar bone and periodontal status in peritoneal dialysis patients[J]. Front Physiol, 2021, 12: 759056.
[24]	Yang F, Shu C J, Wang C J, et al. Meta-analysis of the association between chronic periodontitis and chronic kidney disease[J]. World J Clin Cases, 2024, 12(22): 5094-5107.
[25]	Reiss A B, Miyawaki N, Moon J, et al. CKD, arterial calcification, atherosclerosis and bone health: inter-relationships and controversies[J]. Atherosclerosis, 2018, 278: 49-59.
[26]	Kates D M, Sherrard D J, Andress D L. Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure[J]. Am J Kidney Dis, 1997, 30(6): 809-813.
[27]	Pazianas M, Miller P D. Osteoporosis and chronic kidney disease-mineral and bone disorder (CKD-MBD): back to basics[J]. Am J Kidney Dis, 2021, 78(4): 582-589.
[28]	Miller P D. Chronic kidney disease and the skeleton[J]. Bone Res, 2014, 2: 14044.
[29]	Neven E, Vervaet B, Brand K, et al. Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder[J]. Kidney Int, 2018, 94(1): 102-113.
[30]	Chen H W, Zhou Y N, Liu Y L, et al. Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis[J]. Oral Dis, 2025, 31(1): 264-277.
[31]	Liu W C, Wu C C, Lim P S, et al. Effect of uremic toxin-indoxyl sulfate on the skeletal system[J]. Clin Chim Acta, 2018, 484: 197-206.
[32]	Nii-Kono T, Iwasaki Y, Uchida M, et al. Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells[J]. Kidney Int, 2007, 71(8): 738-743.
[33]	Hruska K. New concepts in renal osteodystrophy[J]. Nephrol Dial Transplant, 1998, 13(11): 2755-2760.
[34]	Gonnelli S, Montagnani A, Caffarelli C, et al. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANK-L) serum levels in patients on chronic hemodialysis[J]. J Endocrinol Investig, 2005, 28(8): 534-539.
[35]	Hsu S N, Stephen L A, Phadwal K, et al. Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder[J]. Kidney Int, 2025, 107(6): 1017-1036.
[36]	Mazzaferro S, Bagordo D, de Martini N, et al. Inflammation, oxidative stress, and bone in chronic kidney disease in the osteoimmunology era[J]. Calcif Tissue Int, 2021, 108(4): 452-460.
[37]	Evenepoel P, Stenvinkel P, Shanahan C, et al. Inflammation and gut dysbiosis as drivers of CKD-MBD[J]. Nat Rev Nephrol, 2023, 19(10): 646-657.
[38]	Chen N X, Srinivasan S, O'Neill K, et al. Effect of advanced glycation end-products (AGE) lowering drug ALT-711 on biochemical, vascular, and bone parameters in a rat model of CKD-MBD[J]. J Bone Miner Res, 2020, 35(3): 608-617.
[39]	Hibbard L M, Liu S, Marambio Y G, et al. Multi-tissue spatial transcriptomics identified simultaneous responses to oxidative stress and apoptosis in parallel with tissue-specific reprogramming in modeled chronic kidney disease-mineral and bone disorder[J]. JBMR Plus, 2025, 9(12): ziaf161.
[40]	Evenepoel P, Jørgensen H S, Bover J, et al. Recommended calcium intake in adults and children with chronic kidney disease: a European consensus statement[J]. Nephrol Dial Transplant, 2024, 39(2): 341-366.
[41]	Gutiérrez O M. Recent advances in the role of diet in bone and mineral disorders in chronic kidney disease[J]. Curr Osteoporos Rep, 2021, 19(6): 574-579.
[42]	Stremke E R, Biruete A, Hill Gallant K M. Dietary protein intake and bone across stages of chronic kidney disease[J]. Curr Osteoporos Rep, 2020, 18(3): 247-253.
[43]	Bacchetta J, Harambat J, Cochat P, et al. The consequences of chronic kidney disease on bone metabolism and growth in children[J]. Nephrol Dial Transplant, 2012, 27(8): 3063-3071.
[44]	Cevik E C, Erel C T, Ozcivit Erkan I B, et al. Chronic kidney disease and menopausal health: an EMAS clinical guide[J]. Maturitas, 2025, 192: 108145.
[45]	Suzuki H, Kondo K. Chronic kidney disease in postmenopausal women[J]. Hypertens Res, 2012, 35(2): 142-147.
[46]	Vorland C J, Lachcik P J, Swallow E A, et al. Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats[J]. Sci Rep, 2019, 9(1): 7936.
[47]	Toejing P, Myint O, Leelahavanichkul A, et al. Nephrectomy induces severe bone loss in mice expressing constitutively active TGFβ receptor type Ⅰ[J]. Int J Mol Sci, 2025, 26(6): 2704.
[48]	Sugatani T. Systemic activation of activin a signaling causes chronic kidney disease-mineral bone disorder[J]. Int J Mol Sci, 2018, 19(9): 2490.
[49]	Xie T, Yang Z L, Dai G Y, et al. Evaluation of the oral health status in Chinese hemodialysis patients[J]. Hemodial Int, 2014, 18(3): 668-673.
[50]	Palmeira E, de Liz Pérez-Losada F, Díaz-Flores-García V, et al. Prevalence of oral infections in chronic kidney disease patients: a cross-sectional study[J]. Oral Dis, 2024, 30(4): 2708-2715.
[51]	Lins P J B, Andrade N S, Caliento R, et al. Alveolar bone healing patterns in chronic kidney failure and kidney transplant recipients: a pixel intensity and fractal analyses[J]. Spec Care Dentist, 2025, 45(1): e13065.
[52]	常雪梅, 任小华, 杨晓民. 尿毒症血液透析患者拔牙对策[J]. 口腔医学, 2004, 24(2): 82-83.
	Chang X M, Ren X H, Yang X M. Countermeasures of tooth-extraction for patients with uremia on dialysis[J]. Journal of Stomatology, 2004, 24(2): 82-83.
[53]	Figueiredo M A, Andrade N S, Blanco Carrión A, et al. Bleeding during tooth extraction in patients with chronic kidney disease: a cross-sectional pilot study[J]. Oral Dis, 2024, 30(4): 2617-2624.
[54]	喻瑶, 李巧文, 刘志明, 等. 慢性肾脏病导致全身多系统疾病患者拔牙1例[J]. 口腔医学研究, 2023, 39(7): 652-653.
	Yu Y, Li Q W, Liu Z M, et al. Tooth extraction for patient with multisystem disease caused by chronic kidney disease: a case report[J]. Journal of Oral Science Research, 2023, 39(7): 652-653.
[55]	Ishimaru M, Ono S, Iwagami M, et al. Risk of surgical site infections after tooth extraction in CKD: a retrospective real-world study in Japan[J]. Clin J Am Soc Nephrol, 2025, 20(4): 582-584.
[56]	Yuan Q, Xiong Q C, Gupta M, et al. Dental implant treatment for renal failure patients on dialysis: a clinical guideline[J]. Int J Oral Sci, 2017, 9(3): 125-132.
[57]	Scarano A, Mortellaro C, Alla I, et al. Oral surgery and dental implants in patients with chronic kidney disease: scoping review for oral health status[J]. Discov Med, 2024, 36(184): 874-881.
[58]	杨震, 汤兵, 孟昭业, 等. 肾衰患者血透期间接受拔牙手术的临床观察[J]. 实用口腔医学杂志, 1998, 14(2): 150.
	Yang Z, Tang B, Meng Z Y, et al. Clinical observation on patients with renal failure undergoing tooth extraction during hemodialysis[J]. Journal of Practical Stomatology, 1998, 14(2): 150.
[59]	Zou H W, Zhao X F, Sun N Y, et al. Effect of chronic kidney disease on the healing of titanium implants[J]. Bone, 2013, 56(2): 410-415.
[60]	Sun N Y, Guo Y C, Liu W Q, et al. FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice[J]. Sci Rep, 2015, 5: 8304.
[61]	杨震, 寿柏泉, 朱文, 等. 肾衰透析患者拔牙的临床研究[J]. 医学研究生学报, 2001, 14(4): 338-340.
	Yang Z, Shou B Q, Zhu W, et al. Clinical studies of extracting tooth in dialysis patients[J]. Journal of Medical Postgraduates, 2001, 14(4): 338-340.

Potential mechanism	Key factor	Pathway and effect	Reference
Calcium-phosphate metabolism imbalance	PTH, FGF-23, Klotho, 1, 25(OH)₂D, calcium, phosphate	Declining renal function triggers hyperphosphatemia and hypocalcemia, inducing secondary hyperparathyroidism	[17-21]
		Dysregulation of the FGF-23/Klotho pathway exacerbates mineral metabolism imbalance
		Vitamin D deficiency impairs calcium absorption and disrupts PTH regulation
		IS accumulation induces oxidative stress, disrupting the balance between osteoblasts and osteoclasts
Uremic toxin-induced damage	IS, AhR, Wnt/β-catenin, SOST, DKK1	IS activates the AhR pathway, thereby impairing bone formation and mineralization	[22-33]
		IS-induced PTH resistance contributes to impaired bone formation
		IS induces osteocyte dysfunction, leading to bone loss
		Inflammation promotes osteoclast activation and osteoblast inhibition through the RANKL/OPG and NF-κB pathways
Inflammation and oxidative stress	IL-6, TNF-α, IL-17, NF-κB, RAGE	Oxidative stress induces ROS-mediated osteoblast damage and aggravates PTH resistance	[28-39]
		AGEs promote apoptosis and oxidative stress, thereby aggravating bone fragility
		Severely impaired calcium absorption and utilization
Nutritional and metabolic disorder	Calcium, phosphate, vitamin D, FGF-23, PTH	High phosphorus intake disrupts bone remodeling	[34-44]
		Protein intake exerts complex effects on bone metabolism
		Vitamin D deficiency and muscle loss synergistically suppress bone formation
		Estrogen loss accelerates bone loss and fragility
Hormonal and growth factor disorder	Estrogen, activin A, SMAD2, TGF-β, TβRI	Activation of the TGF-β pathway promotes fibrosis and disrupts bone homeostasis	[40-44]
		Activin A promotes osteoclastogenesis and inhibits bone formation
		Inflammatory and hormonal signals interact to exacerbate bone damage

Potential mechanism	Key factor	Pathway and effect	Reference
Calcium-phosphate metabolism imbalance	PTH, FGF-23, Klotho, 1, 25(OH)₂D, calcium, phosphate	Declining renal function triggers hyperphosphatemia and hypocalcemia, inducing secondary hyperparathyroidism	[17-21]
		Dysregulation of the FGF-23/Klotho pathway exacerbates mineral metabolism imbalance
		Vitamin D deficiency impairs calcium absorption and disrupts PTH regulation
		IS accumulation induces oxidative stress, disrupting the balance between osteoblasts and osteoclasts
Uremic toxin-induced damage	IS, AhR, Wnt/β-catenin, SOST, DKK1	IS activates the AhR pathway, thereby impairing bone formation and mineralization	[22-33]
		IS-induced PTH resistance contributes to impaired bone formation
		IS induces osteocyte dysfunction, leading to bone loss
		Inflammation promotes osteoclast activation and osteoblast inhibition through the RANKL/OPG and NF-κB pathways
Inflammation and oxidative stress	IL-6, TNF-α, IL-17, NF-κB, RAGE	Oxidative stress induces ROS-mediated osteoblast damage and aggravates PTH resistance	[28-39]
		AGEs promote apoptosis and oxidative stress, thereby aggravating bone fragility
		Severely impaired calcium absorption and utilization
Nutritional and metabolic disorder	Calcium, phosphate, vitamin D, FGF-23, PTH	High phosphorus intake disrupts bone remodeling	[34-44]
		Protein intake exerts complex effects on bone metabolism
		Vitamin D deficiency and muscle loss synergistically suppress bone formation
		Estrogen loss accelerates bone loss and fragility
Hormonal and growth factor disorder	Estrogen, activin A, SMAD2, TGF-β, TβRI	Activation of the TGF-β pathway promotes fibrosis and disrupts bone homeostasis	[40-44]
		Activin A promotes osteoclastogenesis and inhibits bone formation
		Inflammatory and hormonal signals interact to exacerbate bone damage