Care of patients with diabetes should include assessment of bone health. The extension of the average life expectancy of people with diabetes, which has accompanied improvements in medical care, has also increased the significance of osteoporosis. In addition to the usual causes of osteoporosis associated with aging, bone health is also compromised by diabetes. Studies on bone involvement in patients with diabetes mellitus have generated conflicting results, largely because of the pathogenetic complexity of the condition. It is now clear that patients with type 1 diabetes have lower bone mineral density (BMD) and a higher risk of fractures. Evidence is emerging that patients with type 2 diabetes who have complications are also at increased risk of certain types of osteoporotic fractures, despite having a higher BMD when compared to patients with type 1 diabetes. Although many factors, including number and type of falls, visual impairment, neuropathy, and reduced muscle strength, influence the probability of fractures, the most significant factor seems to be the strength of the bone itself. Thus, sarcopenia, a reduction in muscle mass and muscle strength, is considered one of the main determinants of bone fragility. The aim of this review is to examine the occurrence of osteoporosis in type 1 and type 2 diabetes.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes; estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047–53.
United Nations Population Division, Department of Economic and Social Affairs. World Urbanization Prospects: 1999 Revision. New York: United Nations Population Division, Department of Economic and Social Affairs, 1999.
Harris MI, Regal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the Third National Health and Nutrition Examination Survey, 1988–98. Diabetes Care 1998; 21: 518–24.
Onkamo P, Väänänen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of Type I diabetes — the analysis of the data on published incidence trends. Diabetologia 1999; 42: 1395–403.
EURODIAB ACE Study Group. Variation and trends in incidence of childhood diabetes in Europe. Lancet 2000; 355: 873–6.
Green A, Patterson CC. Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia 2001; 44 (Suppl 3): B3–8.
Tuomilehto J, Virtala E, Karvonen M, et al. Increase in incidence of insulin-dependent diabetes mellitus among children in Finland. Int J Epidemiol 1995; 24: 984–92.
Garnder SG, Bingley PJ, Sawtell PA, Weeks S, Gale EA. Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis. The Bart’s-Oxford Study Group. BMJ 1997; 315: 713–7.
Dahlquist G, Mustonen L. Analysis of 20 years of prospective registration of childhood onset diabetes, time trends, and birth cohort effects. Swedish Childhood Diabetes Study Group. Acta Paediatr 2000; 89: 1231–7.
Fagot-Campagna A, Pettitt DJ, Engelgau MM, et al. Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 2000; 136: 664–72.
International Diabetes Federation. Diabetes atlas, 2nd ED. Brussels: International Diabetes Federation, 2003.
World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: report of a WHO study group. Geneva: World Health Organisation, 1994 (Tec. Rep. Ser., n. 843).
Looker A, Orwoll E, Johnston CC, et al. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 1997; 12: 1761–8.
Melton LJ, III. Who has osteoporosis? A conflict between clinical and public health perspectives. J Bone Miner Metab 2000; 15: 2309–14.
Gullberg B, Johnell O, Kanis J. World-wide projections for hip fracture. Osteoporosis Int 1997; 7: 407–13.
Ray NF, Chan JK, Thamer M, Melton LJKKK. Medical expenditures for the treatment of osteoporotic fracture in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 1997; 12: 24–35.
Maggi S, Noale M, Giannini S, et al. Quantitative heel ultrasound in a population-based study in Italy and its relationship with fracture history: the ESOPO study. Osteoporos Int 2006; 17: 237–44.
12a Commissione Permanente del Senato della Repubblica (Igiene e Sanità), sui problemi socio-sanitari connessi alla patologia osteoporotica. Rome: Italian Senate.
Albright F, Reifenstein EC. Parathyroid glands and metabolic bone disease. Selected studies. Baltimore: Williams and Wilkins Company, 1948: 150.
Meema HE, Meema S. The relationship of diabetes mellitus and body weight to osteoporosis in elderly females. Can Med Ass J 1967; 96: 132–9.
Kayath MJ, Tavares EF, Dib SA, Vieria JGH. Prospective bone mineral density evaluation in patients with insulin-dependent diabetes mellitus. J Diabetes Complications 1998; 12: 133–9.
Piepkorn B, Kann P, Forst T, Andreas J, Pfützner A, Beyer J. Bone mineral density and bone metabolism in diabetes mellitus. Horm Metab Res 1997; 29: 584–91.
De Leeuw I, Mulkens N, Vertommen J, Abs R. A histo-morphometric study on the trabecular bone of diabetic subjects (Abstract). Diabetologia 1976; 12: 385–6.
McNair P, Madsbad S, Christiansen C, Faber OK, Transbol I, Binder C. Osteopenia in insulin treated diabetes mellitus. Diabetologia 1978; 15: 87–90.
Levin ME; Boisseau VC, Avioli LV. Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes. N Engl J Med 1976; 294: 241–5.
Pascual J, Argente J, Lopez MB, et al. Bone mineral density in children and adolescents with diabetes mellitus type 1 of recent onset. Calcif Tissue Int 1998; 62: 31–5.
Liu EY, Wactawski-Wende J, Donahue RP, Dmochowski J, Hovey KM, Quattrin T. Does low bone mineral density start in post-teenage years in women with type 1 diabetes? Diabetes Care 2003; 26: 2365–9.
Ingberg CM, Palmer M, Aman J, Arvidsson B, Schvarcz E, Berne C. Body composition and bone mineral density in longstanding type 1 diabetes. J Intern Med 2004; 255: 392–8.
Bridges MJ, Moochhala SH, Barbour J, Kelly CA. Influence of diabetes on peripheral bone mineral density in men: a controlled study. Acta Diabetol 2005; 42: 82–6.
López-Ibarra PJ, Pastor MM, Escobar-Jiménez F, et al. Bone mineral density at time of clinical diagnosis of adult-onset type 1 diabetes mellitus. Endocr Pract 2001; 7: 346–51.
Kemink SA, Hermus AR, Swinkels LM, Lutterman JA, Smals AG. Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology. J Endocrinol Invest 2000; 23: 295–303.
Tuominen JT, Impivaara O, Puukka P, Rönnemaa T. Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 1999; 22: 1196–200.
Hampson G, Evans C, Petitt RJ, et al. Bone mineral density, collagen type 1 alpha 1 genotypes and bone turnover in premenopausal women with diabetes mellitus. Diabetologia 1998; 41: 1314–20.
Selby PL. Osteopenia and diabetes. Diabet Med 1988; 5: 423–8.
Roe TF, Mora S, Costin G, Kaufman F, Carlson ME, Gilsanz V. Vertebral bone density in insulin-dependent diabetic children. Metabolism 1991; 40: 967–71.
Forsen L, Meyer HE, Midthjell K, Edna TH. Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 1999; 42: 920–5.
Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Diabetes and risk of fracture: the Blue Mountains Eye Study. Diabetes Care 2001; 24: 1198–203.
Melchior TM, Sorensen H, Torp-Pedersen C. Hip and distal arm fracture rates in peri- and postmenopausal insulin-treated diabetic females. J Intern Med 1994; 236: 203–8.
Meyer HE, Tverdal A, Falch JA. Risk factors for hip fracture in middle-aged Norwegian women and men. Am J Epidemiol 1993; 137: 1203–11.
Nicodemus KK, Folsom AR. Type 1 and type 2 diabetes and incident hip fractures in post-menopausal women. Diabetes Care 2001; 24: 1192–7.
Thrailkill KM, Lumpkin CK Jr, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 2005; 289: E735–45.
Bouillon R. Diabetic bone disease. Low turnover osteoporosis related to decreased IGF-I production. Verh K Acad Geneeskd Belg 1992; 54: 365–91.
Verhaeghe J, Van Herck E, Visser WJ, et al. Bone and mineral metabolism in BB rats with long-term diabetes. Diabetes 1990; 39: 477–82.
Kitamura T, Kitamura Y, Nakae J, et al. Mosaic analysis of insulin receptor function. J Clin Invest 2004; 113: 209–19.
Jiang J, Lichtler AC, Gronowicz GA, et al. Transgenic mice with osteoblast-targeted insulin-like growth factor-I show increased bone remodeling. Bone 2006; 39: 494–504.
Bouillon R. Diabetic bone disease. Calcif Tissue Int 1991; 48: 155–60.
Waud CE, Marks Jr SC, Lew R, Baran DT. Bone-mineral density in the femur and lumbar vertebrae decreases after twelve weeks of diabetes in spontaneous diabetic-prone BB/Worcester rats. Calcif Tissue Int 1994; 54: 237–40.
Bjorgaas M, Haug E, Johnsen HJ. The urinary excretion of deoxypyridinium cross-links is higher in diabetic than in nondiabetic adolescents. Calcif Tissue Int 1999; 65: 121–4.
Loder RT. The influence of diabetes mellitus on the healing of closed fractures. Clin Orthopedics 1988; 232: 210–6.
Krakauer JC, McKenna MJ, Rao DS, Whitehouse FW. Bone mineral density in diabetes. Diabetes Care 1997; 20: 1339–40.
Munoz-Torres M, Fódar E, Escobar-Jiménez F, López-Ibarra PJ, Luna JD. Bone mineral density measured by dual X-ray absorptiometry in Spanish patients with insulin-dependent diabetes mellitus. Calcif Tissue Int 1996; 58: 316–9.
Kayath MJ, Dib SA, Vieiaa JG. Prevalence and magnitude of osteopenia associated with insulin-dependent diabetes mellitus. J Diabetes Complications 1994; 8: 97–104.
Mathiassen B, Nielsen S, Ditzel J, Rodbro P. Long-term bone loss in insulin-dependent diabetes mellitus. J Intern Med 1990; 227: 325–7.
Rix M, Andreassen H, Eskildsen P. Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care 1999; 22: 827–31.
Forst T, Pfützner A, Kann P, et al. Peripheral osteopenia in adult patients with insulin-dependent diabetes mellitus. Diabet Med 1995; 12: 874–9.
Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM. Bone loss and bone turnover in diabetes. Diabetes 1995; 44: 775–82.
Campos Pastor MM, López-Ibarra PJ, Escobar-Jiménez F, Serrano Pardo MD, Garcia-Cervignón AG. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int 2000; 11: 455–9.
Raskin P, Stevenson MR, Barilla DE, Pak CY. The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol (Oxf) 1978; 9: 329–35.
Nagasaka S, Murakami T, Ucchikawa T, Ishikawa SE, Saito T. Effect of glycemic control on calcium and phosphorus handling and parathyroid hormone level in patients with non-insulin-dependent diabetes mellitus. Endocr J 1995; 42: 377–83.
Okazaki R, Totsuka Y, Hamano K, et al. Metabolic improvement of poorly controlled non-insulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 1997; 82: 2915–20.
Gunczler P, Lanes R, Paoli M, Martinis R, Villaroel O, Weisinger JR. Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2001; 14: 525–8.
Clowes JA, Khosla S, Eastell R. Potential role of pancreatic and enteric hormones in regulating bone turnover. J Bone Miner Res 2005; 20: 1497–506.
Henriksen DB, Alexandersen P, Bjamason NH, et al. Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res 2003; 18: 2180–9.
Bollag RJ, Zhong Q, Phillips P, et al. Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors. Endocrinology 2000; 141: 1228–35.
Bollag RJ, Zhong Q, Ding KH, et al. Glucose-dependent insulinotropic peptide is an integrative hormone with osteotropic effects. Mol Cell Endocrinol 2001; 177: 35–41.
Kong YY, Boyle WJ, Penninger JM. Osteoprotegerin ligand: a regulator of immune responses and bone physiology. Immunol Today 2000; 21: 495–502.
Isaia G, Bodrato L, Carlevatto V, Musetta M, Salamono G, Molinatti, GM. Osteoporosis in type II diabetes. Acta Diabetol Lat 1987; 24: 305–10.
Haffner SM, Bauer RI. The association of obesity and glucose and insulin concentrations with bone density in premenopausal and postmenopausal women. Metabolism 1993; 6: 735–8.
Buysschaert M, Cauwe F, Jarmart J, et al. Proximal femur density in type I and type II diabetic patients. Diabete Metab 1992; 18: 32–7.
Kao CH, Tsou CT, Chen CC Wang SJ. Bone-mineral density in patients with non-insulin-dependent diabetes mellitus by dual photon absorptiometry. Nucl Med Commun 1993; 14: 373–7.
Okuno YY, Nishizawa, Sekiya K, Hagiwara S, Miki T, Horii H. Total and regional bone mineral content in patients with non-insulin dependent diabetes mellitus. J Nutr Sci Vitamnol 1991; 37: 43–9.
Sosa M, Dominguez M, Navarro MC, et al. Bone mineral metabolism is normal in non-insulin-dependent diabetes mellitus. J Diabetes Complications 1996; 10: 201–5.
Avery L. Diabetes mellitus type 1 and 2: an overwiew. Nursing Stand 1998; 13: 35–8.
Barett-Connor E, Holbrook TL. Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. JAMA 1992; 268: 3333–7.
Wakasuigi M, Wakao M, Tawata M, Gan MN, Koizumi K, Onaya T. Bone-mineral density measured by dual energy X-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus. Bone 1993; 14: 29–33.
van Daele PLA, Stolk RP, Burger H, et al. Bone density in non-insulin-dependent diabetes mellitus: the Rotterdam Study. Ann Intern Med 1995; 122: 409–14.
Johnston CC, Hui SL, Longcope C. Bone mass and sex steroid concentrations in postmenopausal Caucasian diabetics. Metabolism 1985; 34: 544–50.
Dobnig H, Piswanger-Sölkner JC, Roth M, et al. Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 2006; 91: 3355–63.
Cumming RG, Nevitt MC, Cummings SR. Epidemiology of hip fractures. Epidemiol Rev 1997; 19: 244–57.
Heath H, Melton LJ, Chu CP. Diabetes mellitus and risk of skeletal fracture. N Engl J Med 1980; 303: 567–70.
Menczel J, Makin M, Robin G, Jaye I, Naor E. Prevalence of diabetes mellitus in Jerusalem. Israel J Med Sci 1972; 8: 918–9.
Paganini-Hill A, Ross RK, Gerkings VR, Henderson BE, Arthur M, Mack TM. Menopausal estrogen therapy and hip fractures. Ann Intern Med 1981; 95: 28–31.
Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. N Engl J Med 1995; 332: 767–73.
Schwartz AV, Sellmeyer DE, Ensrud KE, et al. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 2001; 86: 32–8.
Meier CR, Schlienger RG, Kraenzlin ME, Schlegel B, Jick H. HMG-CoA reductase inhibitors and the risk of fractures. JAMA 2000; 283: 3205–10.
LaCroix AZ, Cauley JA, Pettinger M, et al. Statin menopausal women: results from the Women’s Health Initiative observation- al study. Ann Intern Med 2004; 139: 97–104.
Rzonca SO, Suva LJ, Gaddy D, Montague DC, Lecka-Czernik B. Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 2004; 145: 401–6.
Lecka-Czernik B, Suva LJ, Gaddy D, Rzonca SO. Glitazones, the anti-diabetic PPAR-gamma agonists, pose a significant risk of bone loss: differential effects of rosiglitazone and netoglitazone (Abstract). J Bone Miner Res 2003; 18 (Suppl. 2): S24.
Kaye SA, Folsom AR, Sprafka JM, Prineas RJ, Wallace RB. Increased incidence of diabetes mellitus in relation to abdominal adiposity in older women. J Clin Epidemiol 1991; 44: 329–34.
Vogt MT, Cauley JA, Kuller LH, Nevitt MC. Bone mineral density and blood flow to the lower extremities. J Bone Miner Res 1997; 12: 283–9.
Nevitt MC. Epidemiology of osteoporosis. Rheum Dis Clinc North Am 1994; 2: 535–9.
Wallace C, Reiber GE, LeMaster J, et al. Incidence of falls, risk factors for falls, and fall-related fractures in individuals with diabetes and a prior foot ulcer. Diabetes Care 2002; 24: 1983–6.
Thalassinos NC, Hadjiyanni P, Tzaneia M, Alevizaki, C, Philokiprou D. Calcium metabolism in diabetes mellitus: effect of improved blood glucose control. Diabet Med 1993; 10: 341–4.
Selby PI, Shearing PA, Marshall SM. Hydroxyproline excretion is increased in diabetes mellitus and related to the presence of microalbuminuria. Diabet Med 1995; 12: 240–3.
Stepán J, Havránek T, Formánková J, Skrha J, Skrha F, Pacovsky V. Bone isoenzyme of serum alkaline phosphatase in diabetes mellitus. Clin Chim Acta. 1980; 105: 75–81.
Bouillon R, Bex M, Van Herck E, et al. Influence of age, sex and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus. J Clin Endocrinol Metab 1995; 80: 1194–202.
Gallacher SJ, Fenner JA, Fisher BM, et al. An evaluation of bone density and turnover in premenopausal women with type 1 diabetes mellitus. Diabet Med 1993; 10: 129–33.
Sayinalp S, Gedik O, Koray Z. Increasing serum osteocalcin after glycemic control in diabetic men. Calcif Tissue Int 1995; 57: 422–5.
Ryo O, Yasuo T, Kumiko H, et al. Metabolic improvemet of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 1997; 82: 2915–21.
Stein GS, Lian JB. Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev 1993; 14: 424–42.
Tomasek JJ, Meuers SW, Basinger JB, Green DJ, Shew RL. Diabetic and age-related enhancement of collagen-linked fluorescence in cortical bones of rats. Life Sci 1994; 55: 855–61.
Katayama Y, Akatsu T, Yamamoto M, Kugai N, Nagata N. Role of nonenzymatic glycosylation of type I collagen in diabetic osteopenia. J Bone Miner Res 1996; 11: 931–7.
Fong Y, Edelstein D, Wang EA, Brownlee M. Inhibition of matrix-induced bone differentiation by advanced glycation end-products in rats. Diabetologia 1993; 36: 802–7.
Miyata T, Notoya K, Yoshida K, et al. Advanced glycation end- products enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted subcutaneously with devitalised bone particles. J Am Soc Nephrol 1997; 8: 260–70.
Takagi M, Kasayama S, Yamamoto T, et al. Advanced glycation endproducts stimulate interleukin-6 production by human bonederived cells. J Bone Miner Res 1997; 12: 439–46.
Saito M, Fujii K, Mori Y, Marumo K. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 2006; 17: 1514–23.
Schäffler A, Müller-Ladner U, Schölmerich J, Büchler C. Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev 2006; 27: 449–67.
Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 1999; 140: 1630–8.
Holloway WR, Collier FM, Aitken CJ, et al. Leptin inhibits osteoclast generation. J Bone Miner Res 2002; 17: 200–9.
Thommesen L, Stunes AK, Monjo M, et al. Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism. J Cell Biochem 2006; 99: 824–34.
Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96: 939–49.
Nagi DK, Hendra TJ, Ryle AJ, et al. The relationships of concentrations of insulin, intact proinsulin and 32–33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-depen- dent) diabetic subjects. Diabetologia 1990; 33: 532–7.
Wakasugi M, Wakao RM, Tawata M, Gan N, Koizumi K, Onaya T. Bone mineral density in patients with hyperthyroidism measured by dual energy X-ray absorptiometry. Clin Endocrinol (Oxf) 1994; 40: 281.
Jehle PM, Jehle DR, Mohan S, Böhm BO. Serum levels of insulin-like growth factor system components and relationships to bone metabolism in type 1 and type 2 diabetes mellitus patients. J Endocrinol 1998; 159: 297–306.
Espallargues M, Sampietro-Colom L, Estrada MD, et al. Identifying bone-mass-related risk factors for fracture to guide bone densitometry measurements: a systematic review of the literature. Osteoporosis Int 2001; 12: 811–22.
Ferrucci L, Russo Cr, Lauretani F, Bandinelli S, Guralnik JM. A role for sarcopenia in late-life osteoporosis. Aging Clin Exp Res 2002; 14: 1–4.
Maggi S, Lauretani F, Ferrucci L, et al. The quality of bone: a “magic natural alloy” Aging Clin Exp Res 2004: 16: 3–9.
About this article
Cite this article
Saller, A., Maggi, S., Romanato, G. et al. Diabetes and osteoporosis. Aging Clin Exp Res 20, 280–289 (2008). https://doi.org/10.1007/BF03324857
- quality of bone