The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease

Sun, H. et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract. 183, 109119 (2022).
Google Scholar
Fan, Y., Wei, F., Lang, Y. & Liu, Y. Diabetes mellitus and risk of hip fractures: a meta-analysis. Osteoporos. Int. 27, 219–228 (2016).
Google Scholar
Vestergaard, P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes – a meta-analysis. Osteoporos. Int. 18, 427–444 (2007).
Google Scholar
Dytfeld, J. & Michalak, M. Type 2 diabetes and risk of low-energy fractures in postmenopausal women: meta-analysis of observational studies. Aging Clin. Exp. Res. 29, 301–309 (2017).
Google Scholar
Yamamoto, M., Yamaguchi, T., Yamauchi, M., Kaji, H. & Sugimoto, T. Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J. Bone Miner. Res. 24, 702–709 (2009).
Google Scholar
Moayeri, A. et al. Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis. Ther. Clin. Risk Manag. 13, 455–468 (2017).
Google Scholar
Vilaca, T. et al. The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: a systematic review and meta-analysis update. Bone 137, 115457 (2020).
Google Scholar
Janghorbani, M., Van Dam, R. M., Willett, W. C. & Hu, F. B. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am. J. Epidemiol. 166, 495–505 (2007).
Google Scholar
Schwartz, A. V. Epidemiology of fractures in type 2 diabetes. Bone 82, 2–8 (2016).
Google Scholar
Weber, D. R., Haynes, K., Leonard, M. B., Willi, S. M. & Denburg, M. R. Type 1 diabetes is associated with an increased risk of fracture across the life span: a population-based cohort study using The Health Improvement Network (THIN). Diabetes Care 38, 1913–1920 (2015).
Google Scholar
Wang, B. et al. Unmasking fracture risk in type 2 diabetes: the association of longitudinal glycemic hemoglobin level and medications. J. Clin. Endocrinol. Metab. 107, e1390–e1401 (2022).
Google Scholar
Draghici, A. E., Zahedi, B., Taylor, J. A., Bouxsein, M. L. & Yu, E. W. Vascular deficits contributing to skeletal fragility in type 1 diabetes. Front. Clin. Diabetes Healthcare 4, (2023).
Elger, M., Parpia, A. S. & Whitham, D. in Nutrition in Kidney Disease (eds Burrowes J. D., Kovesdy, C. P. & Byham-Gray L. D.) 175–196 (Springer, 2020).
Ketteler, M. et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int. 92, 26–36 (2017).
Google Scholar
Malluche, H. H., Davenport, D. L., Lima, F. & Monier-Faugere, M. C. Prevalence of low bone formation in untreated patients with osteoporosis. PLoS ONE 17, e0271555 (2022).
Google Scholar
Hygum, K., Starup-Linde, J., Harslof, T., Vestergaard, P. & Langdahl, B. L. Mechanisms in endocrinology: diabetes mellitus, a state of low bone turnover – a systematic review and meta-analysis. Eur. J. Endocrinol. 176, R137–R157 (2017).
Google Scholar
Patsch, J. M. et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J. Bone Miner. Res. 28, 313–324 (2013).
Google Scholar
Meier, C. et al. Biochemical markers of bone fragility in patients with diabetes. J. Clin. Endocrinol. Metab. 108, e923–e936 (2023).
Google Scholar
Lekkala, S. et al. Increased advanced glycation endproducts, stiffness, and hardness in iliac crest bone from postmenopausal women with type 2 diabetes mellitus on insulin. J. Bone Miner. Res. 38, 261–277 (2023).
Google Scholar
Stenderup, K., Justesen, J., Clausen, C. & Kassem, M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33, 919–926 (2003).
Google Scholar
Piccoli, A. et al. Sclerostin regulation, microarchitecture, and advanced glycation end-products in the bone of elderly women with type 2 diabetes. J. Bone Miner. Res. 35, 2415–2422 (2020).
Google Scholar
Miao, J., Brismar, K., Nyrén, O., Ugarph-Morawski, A. & Ye, W. Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care 28, 2850–2855 (2005).
Google Scholar
Shanbhogue, V. V. et al. Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in adult patients with type 1 diabetes mellitus. J. Bone Miner. Res. 30, 2188–2199 (2015).
Google Scholar
Brockstedt, H., Kassem, M., Eriksen, E. F., Mosekilde, L. & Melsen, F. Age- and sex-related changes in iliac cortical bone mass and remodeling. Bone 14, 681–691 (1993).
Google Scholar
Shah, V. N. et al. Type 1 diabetes onset at young age is associated with compromised bone quality. Bone 123, 260–264 (2019).
Google Scholar
Weaver, C. M. et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos. Int. 27, 1281–1386 (2016).
Google Scholar
Cao, J. J. Effects of obesity on bone metabolism. J. Orthop. Surg. Res. 6, 30 (2011).
Google Scholar
Schweiger, B. M., Snell-Bergeon, J. K., Roman, R., McFann, K. & Klingensmith, G. J. Menarche delay and menstrual irregularities persist in adolescents with type 1 diabetes. Reprod. Biol. Endocrinol. : RBE 9, 61 (2011).
Google Scholar
Deltsidou, A. Age at menarche and menstrual irregularities of adolescents with type 1 diabetes. J. Pediatr. Adolesc. Gynecol. 23, 162–167 (2010).
Google Scholar
Thong, E. P. et al. Increased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease. Clin. Endocrinol. 88, 37–43 (2018).
Google Scholar
Mitri, J. & Pittas, A. G. Vitamin D and diabetes. Endocrinol. Metab. Clin. North. Am. 43, 205–232 (2014).
Google Scholar
He, X. et al. Parathyroid hormone is negatively correlated with glycated hemoglobin in newly diagnosed type 2 diabetic patients. Int. J. Endocrinol. 2024, 8414689 (2024).
Google Scholar
ANZDATA Registry. Prevalence of Kidney Failure with Replacement Therapy. 44th Report, Chapter 2. Australia and New Zealand Dialysis and Transplant Registry (2021).
Asamiya, Y., Tsuchiya, K. & Nitta, K. Role of sclerostin in the pathogenesis of chronic kidney disease-mineral bone disorder. Ren. Replacement Ther. 2, 8 (2016).
Google Scholar
Lewiecki, E. M. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases. Ther. Adv. Musculoskelet. Dis. 6, 48–57 (2014).
Google Scholar
Naylor, K. L. et al. Comparison of fracture risk prediction among individuals with reduced and normal kidney function. Clin. J. Am. Soc. Nephrol. 10, 646–653 (2015).
Google Scholar
Naylor, K. L. et al. The three-year incidence of fracture in chronic kidney disease. Kidney Int. 86, 810–818 (2014).
Google Scholar
Tentori, F. et al. High rates of death and hospitalization follow bone fracture among hemodialysis patients. Kidney Int. 85, 166–173 (2014).
Google Scholar
Neal, B., Perkovic, V. & Matthews, D. R. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N. Engl. J. Med. 377, 2099 (2017).
Google Scholar
Perkovic, V. et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N. Engl. J. Med. 380, 2295–2306 (2019).
Google Scholar
Young, T. K. 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, 9998891 (2022).
Google Scholar
Aleksova, J., Ebeling, P., Milat, F. & Elder, G. DXA-derived advanced hip analysis and the trabecular bone score in end stage kidney disease secondary to type 1 diabetes. Eur. J. Endocrinol. 187, 883–892 (2022).
Google Scholar
Cannata-Andía, J. B., Rodriguez García, M. & Gómez Alonso, C. Osteoporosis and adynamic bone in chronic kidney disease. J. Nephrol. 26, 73–80 (2013).
Google Scholar
Hutchison, A. J. et al. Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. Kidney Int. 44, 1071–1077 (1993).
Google Scholar
Modest, J. M., Sheth, H., Gohh, R. & Aaron, R. K. Osteomalacia and renal osteodystrophy. Rhode Isl. Med. J. 105, 22–27 (2022).
Martin, K. J. & González, E. A. Metabolic bone disease in chronic kidney disease. J. Am. Soc. Nephrol. 18, 875–885 (2007).
Google Scholar
Elder, M. et al. Chronic kidney disease-related sarcopenia as a prognostic indicator in elderly haemodialysis patients. BMC Nephrol. 24, 138 (2023).
Google Scholar
Samakkarnthai, P. et al. Determinants of bone material strength and cortical porosity in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 105, e3718–3729 (2020).
Google Scholar
Nickolas, T. L. et al. Rapid cortical bone loss in patients with chronic kidney disease. J. Bone Miner. Res. 28, 1811–1820 (2013).
Google Scholar
Sharma, A. K. et al. Magnetic resonance imaging based assessment of bone microstructure as a non-invasive alternative to histomorphometry in patients with chronic kidney disease. Bone 114, 14–21 (2018).
Google Scholar
Sharma, A. K. et al. Deterioration of cortical bone microarchitecture: critical component of renal osteodystrophy evaluation. Am. J. Nephrol. 47, 376–384 (2018).
Google Scholar
Aleksova, J. et al. Patients with end-stage kidney disease have markedly abnormal cortical hip parameters by dual-energy X-ray absorptiometry. Nephrol. Dial. Transplant. 36, 543–550 (2019).
Google Scholar
Manavalan, J. S. et al. Circulating osteogenic precursor cells in type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 97, 3240–3250 (2012).
Google Scholar
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group KDIGO 2017 Clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Kidney Int. Suppl. 7, 1–59 (2017).
Google Scholar
West, S. L. et al. Bone mineral density predicts fractures in chronic kidney disease. J. Bone Miner. Res. 30, 913–919 (2015).
Google Scholar
Iimori, S. et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients – a single-center cohort study. Nephrol. Dial. Transplant. 27, 345–351 (2012).
Google Scholar
Harvey, N. C. et al. Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. Bone 78, 216–224 (2015).
Google Scholar
Koumakis, E. et al. Trabecular bone score in female patients with systemic sclerosis: comparison with rheumatoid arthritis and influence of glucocorticoid exposure. J. Rheumatol. 42, 228–235 (2015).
Google Scholar
Leslie, W. D., Aubry-Rozier, B., Lamy, O. & Hans, D. Manitoba Bone Density Program TBS (trabecular bone score) and diabetes-related fracture risk. J. Clin. Endocrinol. Metab. 98, 602–609 (2013).
Google Scholar
Yavropoulou, M. P. et al. Bone quality assessment as measured by trabecular bone score in patients with end-stage renal disease on dialysis. J. Clin. Densitom. 20, 490–497 (2016).
Google Scholar
Aleksova, J., Kurniawan, S. & Elder, G. J. The trabecular bone score is associated with bone mineral density, markers of bone turnover and prevalent fracture in patients with end stage kidney disease. Osteoporos. Int. 29, 1447–1455 (2018).
Google Scholar
Naylor, K. L. et al. Trabecular bone score in kidney transplant recipients. Osteoporos. Int. 27, 1115–1121 (2016).
Google Scholar
Kaptoge, S. et al. Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures. J. Bone Miner. Res. 23, 1892–1904 (2008).
Google Scholar
Jamal, S. A., Cheung, A. M., West, S. L. & Lok, C. E. Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease. Osteoporos. Int. 23, 2805–2813 (2012).
Google Scholar
Farr, J. N. et al. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J. Bone Miner. Res. 29, 787–795 (2014).
Google Scholar
Rubin, M. R. et al. Biochemical markers of bone turnover in older adults with type 1 diabetes. J. Clin. Endocrinol. Metab. 107, e2405–e2416 (2022).
Google Scholar
Sinha Gregory, N. et al. Diabetes risk factors and bone microarchitecture as assessed by high-resolution peripheral quantitative computed tomography in adults with long-standing type 1 diabetes. Diabetes Care 47, 1548–1558 (2023).
Google Scholar
Sprague, S. M. et al. Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am. J. Kidney Dis. 67, 559–566 (2016).
Google Scholar
Einbinder, Y., Benchetrit, S., Golan, E. & Zitman-Gal, T. Comparison of intact PTH and bio-intact PTH assays among non-dialysis dependent chronic kidney disease patients. Ann. Lab. Med. 37, 381–387 (2017).
Google Scholar
Drüeke, T. B. Is parathyroid hormone measurement useful for the diagnosis of renal bone disease? Kidney Int. 73, 674–676 (2008).
Google Scholar
Whitlock, R. H. et al. The Fracture Risk Assessment Tool (FRAX(R)) predicts fracture risk in patients with chronic kidney disease. Kidney Int. 95, 447–454 (2018).
Google Scholar
Przedlacki, J. et al. The utility of FRAX(R) in predicting bone fractures in patients with chronic kidney disease on hemodialysis: a two-year prospective multicenter cohort study. Osteoporos. Int. 29, 1105–1115 (2018).
Google Scholar
Przedlacki, J. et al. FRAX prognostic and intervention thresholds in the management of major bone fractures in hemodialysis patients: a two-year prospective multicenter cohort study. Bone 133, 115188 (2020).
Google Scholar
Schwartz, A. V. et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305, 2184–2192 (2011).
Google Scholar
Leslie, W. D. et al. Comparison of methods for improving fracture risk assessment in diabetes: the Manitoba BMD Registry. J. Bone Miner. Res. 33, 1923–1930 (2018).
Google Scholar
Conway, B. N., Long, D. M., Figaro, M. K. & May, M. E. Glycemic control and fracture risk in elderly patients with diabetes. Diabetes Res. Clin. Pract. 115, 47–53 (2016).
Google Scholar
Xi, G., Rosen, C. J. & Clemmons, D. R. IGF-I and IGFBP-2 stimulate AMPK activation and autophagy, which are required for osteoblast differentiation. Endocrinology 157, 268–281 (2016).
Google Scholar
Schwartz, A. V. et al. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care 31, 391–396 (2008).
Google Scholar
Vestergaard, P., Rejnmark, L. & Mosekilde, L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48, 1292–1299 (2005).
Google Scholar
Heaf, J. Metformin in chronic kidney disease: time for a rethink. Perit. Dial. Int. 34, 353–357 (2014).
Google Scholar
Mai, Q. G. et al. Metformin stimulates osteoprotegerin and reduces RANKL expression in osteoblasts and ovariectomized rats. J. Cell Biochem. 112, 2902–2909 (2011).
Google Scholar
Salari-Moghaddam, A., Sadeghi, O., Keshteli, A. H., Larijani, B. & Esmaillzadeh, A. Metformin use and risk of fracture: a systematic review and meta-analysis of observational studies. Osteoporos. Int. 30, 1167–1173 (2019).
Google Scholar
Sarkar, A., Tiwari, A., Bhasin, P. S. & Mitra, M. Pharmacological and pharmaceutical profile of gliclazide: a review. J. Appl. Pharm. Sci. 1, 11–19 (2011).
American Diabetes Association Professional Practice Committee 11. Chronic kidney disease and risk management: standards of care in diabetes – 2024. Diabetes Care 47, S219–S230 (2023).
Google Scholar
Zhu, Z. N., Jiang, Y. F. & Ding, T. Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone 68, 115–123 (2014).
Google Scholar
Alicic, R. Z., Cox, E. J., Neumiller, J. J. & Tuttle, K. R. Incretin drugs in diabetic kidney disease: biological mechanisms and clinical evidence. Nat. Rev. Nephrol. 17, 227–244 (2021).
Google Scholar
Pereira, M. et al. Chronic administration of glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice. Bone 81, 459–467 (2015).
Google Scholar
Cheng, L. et al. Glucagon-like peptide-1 receptor agonists and risk of bone fracture in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetes Metab. Res. Rev. 35, e3168 (2019).
Google Scholar
Hygum, K. et al. Bone resorption is unchanged by liraglutide in type 2 diabetes patients: a randomised controlled trial. Bone 132, 115197 (2020).
Google Scholar
Wheeler, D. C. et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 9, 22–31 (2021).
Google Scholar
Zannad, F. et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 396, 819–829 (2020).
Google Scholar
Bode, B. et al. Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes. Diabetes Obes. Metab. 17, 294–303 (2015).
Google Scholar
Zhou, Z. et al. Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS program. Diabetologia 62, 1854–1867 (2019).
Google Scholar
Li, X. et al. Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: an updated meta-analysis. Diabetes Metab. Res. Rev. 35, e3170 (2019).
Google Scholar
Cheng, L. et al. Risk of bone fracture associated with sodium-glucose cotransporter-2 inhibitor treatment: a meta-analysis of randomized controlled trials. Diabetes Metab. 45, 436–445 (2019).
Google Scholar
Evenepoel, P. et al. Recommended calcium intake in adults and children with chronic kidney disease – a European consensus statement. Nephrol. Dial. Transplant. 39, 341–366 (2024).
Google Scholar
de Oliveira, R. B., Stinghen, A. E. M. & Massy, Z. A. Vitamin K role in mineral and bone disorder of chronic kidney disease. Clin. Chim. Acta 502, 66–72 (2020).
Google Scholar
Chang, X., Xu, S. & Zhang, H. Regulation of bone health through physical exercise: mechanisms and types. Front. Endocrinol. 13, 1029475 (2022).
Google Scholar
Watanabe, K. et al. Home-based exercise and bone mineral density in peritoneal dialysis patients: a randomized pilot study. BMC Nephrol. 22, 98 (2021).
Google Scholar
Khosla, S., Amin, S. & Orwoll, E. Osteoporosis in men. Endocr. Rev. 29, 441–464 (2008).
Google Scholar
Lühe, A. et al. Preclinical evidence for nitrogen-containing bisphosphonate inhibition of farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety. Toxicol. In Vitro 22, 899–909 (2008).
Google Scholar
Iseri, K. et al. Elimination of intravenous alendronate by hemodialysis: a kinetic study. Hemodial. Int. 23, 466–471 (2019).
Google Scholar
Joffe, P. & Henriksen, J. H. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study. Scand. J. Clin. Lab. Invest. 56, 327–337 (1996).
Google Scholar
Eastell, R. et al. Diabetes mellitus and the benefit of antiresorptive therapy on fracture risk. J. Bone Miner. Res. 37, 2121–2131 (2022).
Google Scholar
Miller, P. D. et al. Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials. J. Bone Miner. Res. 20, 2105–2115 (2005).
Google Scholar
Black, D. M. et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J. Clin. Endocrinol. Metab. 85, 4118–4124 (2000).
Google Scholar
Wetmore, J. B., Benet, L. Z., Kleinstuck, D. & Frassetto, L. Effects of short-term alendronate on bone mineral density in haemodialysis patients. Nephrology 10, 393–399 (2005).
Google Scholar
Iseri, K. et al. Effects of denosumab and alendronate on bone health and vascular function in hemodialysis patients: a randomized, controlled trial. J. Bone Miner. Res. 34, 1014–1024 (2019).
Google Scholar
Haarhaus, M. & Evenepoel, P. Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment. Kidney Int. 100, 546–558 (2021).
Google Scholar
Ott, S. M., Malluche, H. H., Jorgetti, V. & Elder, G. J. Importance of bone turnover for therapeutic decisions in patients with CKD-MBD. Kidney Int. 100, 502–505 (2021).
Google Scholar
Allen, M. R. & Aref, M. W. What animal models have taught us about the safety and efficacy of bisphosphonates in chronic kidney disease. Curr. Osteoporos. Rep. 15, 171–177 (2017).
Google Scholar
Persy, V., De Broe, M. & Ketteler, M. Bisphosphonates prevent experimental vascular calcification: treat the bone to cure the vessels? Kidney Int. 70, 1537–1538 (2006).
Google Scholar
Alarkawi, D. et al. Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study. J. Bone Miner. Res. 35, 894–900 (2020).
Google Scholar
Robinson, D. E. et al. Safety of oral bisphosphonates in moderate-to-severe chronic kidney disease: a binational cohort analysis. J. Bone Miner. Res. 36, 820–832 (2021).
Google Scholar
Cummings, S. R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 361, 756–765 (2009).
Google Scholar
Orwoll, E. et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J. Clin. Endocrinol. Metab. 97, 3161–3169 (2012).
Google Scholar
Bone, H. G. et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 5, 513–523 (2017).
Google Scholar
Ferrari, S. et al. Denosumab in postmenopausal women with osteoporosis and diabetes: subgroup analysis of FREEDOM and FREEDOM extension. Bone 134, 115268 (2020).
Google Scholar
Lyu, H. et al. Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study. BMJ 381, e073435 (2023).
Google Scholar
Kiechl, S. et al. Blockade of receptor activator of nuclear factor-κB (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus. Nat. Med. 19, 358–363 (2013).
Google Scholar
Kondegowda, N. G. et al. Osteoprotegerin and denosumab stimulate human beta cell proliferation through inhibition of the receptor activator of NF-κB ligand pathway. Cell Metab. 22, 77–85 (2015).
Google Scholar
Jamal, S. A. et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J. Bone Miner. Res. 26, 1829–1835 (2011).
Google Scholar
Thongprayoon, C. et al. Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies. Osteoporos. Int. 29, 1737–1745 (2018).
Google Scholar
Bird, S. T. et al. Severe hypocalcemia with denosumab among older female dialysis-dependent patients. JAMA 331, 491–499 (2024).
Google Scholar
Dave, V., Chiang, C. Y., Booth, J. & Mount, P. F. Hypocalcemia post denosumab in patients with chronic kidney disease stage 4-5. Am. J. Nephrol. 41, 129–137 (2015).
Google Scholar
Webber, L. et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum. Reprod. 31, 926–937 (2016).
Google Scholar
Matuszkiewicz-Rowinska, J. et al. The benefits of hormone replacement therapy in pre-menopausal women with oestrogen deficiency on haemodialysis. Nephrol. Dial. Transplant. 14, 1238–1243 (1999).
Google Scholar
Manson, J. E. et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 310, 1353–1368 (2013).
Google Scholar
Boardman, H. M. et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst. Rev. 2015, Cd002229 (2015).
Google Scholar
Canonico, M. Hormone therapy and hemostasis among postmenopausal women: a review. Menopause 21, 753–762 (2014).
Google Scholar
Delmas, P. D. et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J. Clin. Endocrinol. Metab. 87, 3609–3617 (2002).
Google Scholar
Nickelsen, T. et al. Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Climacteric 4, 320–331 (2001).
Google Scholar
Ishani, A., Blackwell, T., Jamal, S. A., Cummings, S. R. & Ensrud, K. E. The effect of raloxifene treatment in postmenopausal women with CKD. J. Am. Soc. Nephrol. 19, 1430–1438 (2008).
Google Scholar
Haghverdi, F., Mortaji, S., Soltani, P., Saidi, N. & Farbodara, T. Effect of raloxifene on parathyroid hormone in osteopenic and osteoporotic postmenopausal women with chronic kidney disease stage 5. Iran. J. Kidney Dis. 8, 461–466 (2014).
Google Scholar
Saito, O. et al. Effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes. Int. J. Endocrinol. Metab. 10, 464–469 (2012).
Google Scholar
Aleksova, J. et al. Gonadal hormones in the pathogenesis and treatment of bone health in patients with chronic kidney disease: a systematic review and meta-analysis. Curr. Osteoporos. Rep. 16, 674–692 (2018).
Google Scholar
Adami, S. et al. The efficacy and safety of bazedoxifene in postmenopausal women by baseline kidney function status. Climacteric 17, 273–284 (2014).
Google Scholar
Bhasin, S. et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 103, 1715–1744 (2018).
Google Scholar
Dhindsa, S. et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J. Clin. Endocrinol. Metab. 89, 5462–5468 (2004).
Google Scholar
Grossmann, M. et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J. Clin. Endocrinol. Metab. 93, 1834–1840 (2008).
Google Scholar
Grossmann, M. Low testosterone in men with type 2 diabetes: significance and treatment. J. Clin. Endocrinol. Metab. 96, 2341–2353 (2011).
Google Scholar
Wittert, G. et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 9, 32–45 (2021).
Google Scholar
Carrero, J. J. et al. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol. Dial. Transplant. 26, 184–190 (2011).
Google Scholar
Guvel, S. et al. Calcification of the epididymis and the tunica albuginea of the corpora cavernosa in patients on maintenance hemodialysis. J. Androl. 25, 752–756 (2004).
Google Scholar
Dunkel, L., Raivio, T., Laine, J. & Holmberg, C. Circulating luteinizing hormone receptor inhibitor(s) in boys with chronic renal failure. Kidney Int. 51, 777–784 (1997).
Google Scholar
Brockenbrough, A. T. et al. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Am. J. Kidney Dis. 47, 251–262 (2006).
Google Scholar
Neer, R. M. et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434–1441 (2001).
Google Scholar
Kaufman, J. M. et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos. Int. 16, 510–516 (2005).
Google Scholar
Satterwhite, J. et al. Pharmacokinetics of teriparatide (rhPTH[1-34]) and calcium pharmacodynamics in postmenopausal women with osteoporosis. Calcif. Tissue Int. 87, 485–492 (2010).
Google Scholar
Imai, H. et al. Pharmacokinetics of teriparatide after subcutaneous administration to volunteers with renal failure: a pilot study. Int. J. Clin. Pharmacol. Ther. 52, 166–174 (2014).
Google Scholar
Evenepoel, P. et al. Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism. Osteoporos. Int. 32, 2397–2405 (2021).
Google Scholar
Schwartz, A. V. et al. Teriparatide in patients with osteoporosis and type 2 diabetes. Bone 91, 152–158 (2016).
Google Scholar
Nishikawa, A., Yoshiki, F., Taketsuna, M., Kajimoto, K. & Enomoto, H. Safety and effectiveness of daily teriparatide for osteoporosis in patients with severe stages of chronic kidney disease: post hoc analysis of a postmarketing observational study. Clin. Interv. Aging 11, 1653–1659 (2016).
Google Scholar
Sumida, K. et al. Once-weekly teriparatide in hemodialysis patients with hypoparathyroidism and low bone mass: a prospective study. Osteoporos. Int. 27, 1441–1450 (2016).
Google Scholar
Kritmetapak, K. & Pongchaiyakul, C. Parathyroid hormone measurement in chronic kidney disease: from basics to clinical implications. Int. J. Nephrol. 2019, 5496710 (2019).
Google Scholar
Cejka, D., Kodras, K., Bader, T. & Haas, M. Treatment of hemodialysis-associated adynamic bone disease with teriparatide (PTH1-34): a pilot study. Kidney Blood Press. Res. 33, 221–226 (2010).
Google Scholar
Miller, P. D., Schwartz, E. N., Chen, P., Misurski, D. A. & Krege, J. H. Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos. Int. 18, 59–68 (2007).
Google Scholar
Malluche, H. H., Davenport, D. L., Monier-Faugere, M. C. & Lima, F. Treatment of bone loss in CKD5D: better survival in patients with non-high bone turnover. Clin. Nephrol. 98, 219–228 (2022).
Google Scholar
Miller, P. D. et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA 316, 722–733 (2016).
Google Scholar
Bilezikian, J. P. et al. Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial. Curr. Med. Res. Opin. 35, 2097–2102 (2019).
Google Scholar
Cosman, F. et al. Romosozumab treatment in postmenopausal women with osteoporosis. N. Engl. J. Med. 375, 1532–1543 (2016).
Google Scholar
Hsu, C. P., Maddox, J., Block, G., Bartley, Y. & Yu, Z. Influence of renal function on pharmacokinetics, pharmacodynamics, and safety of a single dose of romosozumab. J. Clin. Pharmacol. 62, 1132–1141 (2022).
Google Scholar
Miller, P. et al. Efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease [abstract OP0297]. Ann. Rheum. Dis. 79 (Suppl. 1), 185 (2020).
Google Scholar
Sato, M. et al. Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study. J. Bone Miner. Metab. 39, 1082–1090 (2021).
Google Scholar
Saito, T. et al. One-year romosozumab treatment followed by one-year denosumab treatment for osteoporosis in patients on hemodialysis: an observational study. Calcif. Tissue Int. 112, 34–44 (2023).
Google Scholar
Saag, K. G., Petersen, J. & Grauer, A. Romosozumab versus alendronate and fracture risk in women with osteoporosis. N. Engl. J. Med. 378, 195–196 (2018).
Google Scholar
Lewiecki, E. M. et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J. Clin. Endocrinol. Metab. 103, 3183–3193 (2018).
Google Scholar
Bovijn, J. et al. Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics. Sci. Transl. Med. 12, eaay6570 (2020).
Google Scholar
Rubin, M. R. & Patsch, J. M. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions. Bone Res. 4, 16001 (2016).
Google Scholar
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