Osteoporosis and Fracture among Patients with Type 1 and Type 2 Diabetes
Eun Joo Park, Seo Yu Hong
Department of Obstetrics and Gynecology, College of Medicine, Eulji University, Seoul, Korea
당뇨병 1형, 2형에서의 골다공증과 골밀도, 골다공증위험인자, 골절
을지대학교 노원을지병원 산부인과학교실 박 은 주․홍 서 유
당뇨병은 골다공증성 골절의 주된 위험요인이다. 당뇨병 환자에게 골다공증의 발생은 당뇨병 치료이상의 큰 경제적, 신체적 부담이 된다. 그러나 아직 당뇨병 환자에게 골다공증의 선별검사, 예방적인 치료가 보편화되어 있지 않다. 당 뇨병과 골다공증의 관계, 당뇨병 1, 2형에 따른 차이 등이 아직 명확하게 규명되어있지 않기 때문이다.
현재 골밀도에 있어서는 당뇨병 1형은 주로 감소한다는 의견에는 일치하나, 당뇨병 2형은 논의의 여지가 있으며 오 히려 1형과 상반되게 변화가 없거나 증가한다고 한다. 그러나 골절에 있어서는 두 형 모두에서 위험성이 증가한다.
당뇨병에서 골다공증성 골절의 위험성이 증가하는 이유는 당뇨병 1형은 오랜 기간 동안 혈당조절의 불량으로 인한 당뇨병성 혈관합병증의 발생으로 골밀도가 감소하게 된다. 당뇨병 2형에서는 비만이 골소실을 막아주는 효과가 있어 오히려 골밀도는 증가할 수 있다. 그러나, 당뇨병 2형 환자들은 고령의 나이, 균형감각의 상실, 심혈관 질환, 관절염, 말초신경증 등과 같은 낙상의 위험요소들을 주로 동반하고 또한, 인슐린 치료 시 저혈당증이 빈번하게 발생하면 낙 상의 위험이 더 증가하여 결과적으로 골절을 증가시킨다.
당뇨병 환자에서 골다공증 선별검사와 예방치료는 그 개개인의 골절위험성을 판별하여 조기에 시행되어져야 한다고 생각한다.
중심단어: 골다공증, 1형, 2형 당뇨병, 골감소증, 골밀도, 골절
Received: November 20, 2009 Revised: December 5, 2009 Accepted: December 30, 2009
Corresponding Author: Seo Yu Hong, Department of Obstetrics and Gynecology, College of Medicine, Eulji University 280-1 Hagae-dong, Nowon-gu, Seoul 139-711, Korea Tel: +82-2-970-8230, Fax: +82-2-970-8231 E-mail: hsy3101@eulji.ac.kr
More than 50 years ago, diabetes mellitus could be associated with a loss of bone mass leading to osteoporosis1. This finding has received a great deal of attention and been investigated by a number of researchers, as osteoporosis is a major health problem, and its occurrence among patients who have diabetes mellitus further increases their burden of disease.
Patients with diabetes mellitus have multiple skeletal disorders, including osteopenia, osteoporosis, Charcot's disease and diffuse idiopathic skeletal hyperostosis (DISH). Specifically, Osteopenia and osteoporosis have been known to be frequent complications of type 1 diabetes mellitus (T1DM) in both children and adults more than type 2 diabetes mellitus (T2DM)2-4. This review will focus on difference of bone mineral density, risk factors of osteoporosis and fracture in patients with each type of diabetes mellitus. We support that osteoporosis screening or prophylactic treatment of osteoporosis in all patients with type 1 and type 2
diabetes mellitus need to be recommended through considering risk factors of osteoporotic fracture.
BONE MINERAL DENSITY (BMD) AND DIABETES MELLITUS 1. Bone mineral density (BMD) in patients
with type 1 diabetes mellitus (T1DM) Osteopenia and osteoporosis have been known to be frequent complications of T1DM in both children and adults2-4. Earlier investigations were carried out using older technologies such as single- or dual-photon absorptiometry, and focused on the appendicular skeleton. BMD analysis is now typically performed using dual X-ray absorptiometry (DXA), a more precise method. The majority of recent studies have confirmed the association between T1DM and decreased BMD in adults5,6 as well as in children7-9. BMD appears to be decreased in both the spine and hip in T1DM. Using DXA, osteopenia is found in about 50～60% of patients with T1DM10,11 while osteoporosis is seen in around 14～20% of cases11,12. A meta-analysis of 80 papers by Vestergaard, assessing the BMD and fracture risk in patients with type 1 or type 2 diabetes, concluded that BMD is decreased in T1DM13, although the vast majority of studies were cross-sectional, limiting the capacity to establish a causal association.
2. Bone mineral density (BMD) in T2DM Earlier studies have given discrepant results for type 1 and type 2 diabetes mellitus, with a decreased BMD in patients with T1DM, but a normal-to-increased BMD in T2DM. Measurements of vertebral or femoral neck BMD by DXA have revealed increased BMD in most patients with T2DM, compared with age-matched subjects without diabetes14-17; the BMD increment persisted even after correction for body weight or body composition and the use of estrogens18. It should be noted, however, that the majority of these studies involved postmenopausal women. The meta-analysis by
Vestergaard also concluded that BMD was increased in T2DM13. Also, body mass index (BMI) appeared to be one of the main determinants of BMD in T2DM.
Nevertheless, the meta-analysis was limited, as infor- mation on BMI was missing in a significant number of studies reviewed. Other publications have reported normal or lower BMD among individuals with T2DM6,19-23. Any discrepancy between the results of these studies and those previously mentioned may be due to differences in the duration, severity and treatment of diabetes, and perhaps also due to the different methods used to measure BMD. Authors have also suggested that an increased BMD, at least in some subgroups of patients with T2DM, could be related to the presence of Forestier's disease (DISH) at the spinal level24.
The associations between type 1 and type 2 diabetes mellitus and BMD are not clear. Nevertheless, patients with type 1 or type 2 diabetes mellitus are at high risk for bone fractures. Major risk factors of osteoporosis for discussing the link between type 1 and type 2 diabetes mellitus and low bone mass is reviewed below.
MAJOR RISK FACTORS OF OSTEOPOROSIS AND DIABETES
MELLITUS
1. Major risk factors of osteoporosis in patients with T1DM
Several studies showed that the presence of micro- and macrovascular diabetic complications as a result of longstanding poor glycemic control rather than long duration predict low BMD in patients with T1DM12,25-30. These include retinopathy12,25,26, peripheral neuropathy27, nephropathy12,28,29, and peripheral vascular disease30. Both diabetic retinopathy and peripheral neuropathy may lower BMD through impaired physical activity and neuromuscular/ skeletal interactions, and enhance the propensity of falls. In one study of 57
patients with T1DM (mean age, 35 years; mean dura- tion; 17 years), osteopenia or osteoporosis was present in 72% of patients with retinopathy, but only in 53% of patients without retinopathy26. Because the incidence of retinopathy is lower in patients with T1DM on intensive insulin therapy compared with conventional therapy, it was concluded that intensive insulin therapy had beneficial effects on bone metabolism. In addition, overt nephropathy (a microalbuminuria of >300 mg/d)12,28, peripheral neuropathy based on biothesiome- try to determine the vibration perception threshold27, and peripheral vascular disease based on pulse status30 were found to be associated with low BMD in patients with T1DM. Men with T1DM tend to be particularly prone to osteopenia or osteoporosis. One study showed that 14% of men, but no women, with T1DM had osteoporosis11, and there was a negative correlation of BMD with duration of T1DM only in men but not in women31. In part, this observation may be caused by the long mean duration of disease of 33 years in this study. In women with T1DM, the use of combined oral contraceptives was positively associated with the BMD at the lumbar spine30, whereas smoking was associated with lower BMD in both women and men with T1DM12. It should be noted that the factors summarized in this section are risk factors for low bone mass, not for fractures.
2. Major risk factors of osteoporosis in patients with T2DM
Several studies suggest that obesity protects against bone loss based on the finding that BMD and BMI are positively correlated in patients with T2DM21,32 and that the BMI in patients with T2DM is negatively asso- ciated with the presence of osteoporosis33. These observations indicate that, in addition to mechanical loading, adipose tissue and its cytokines (“adipokines”) such as leptin, resistin, and adiponectin may modulate BMD increases as discussed below. In fact, one study showed an inverse association between adiponectin
serum levels and BMD at different sites in patients with T2DM34. Other studies have shown that axial BMD is negatively correlated with the duration of T2DM32 and that cortical BMD is negatively correlated with mean hemoglobin A1c serum levels, an index of poor metabolic control22. Despite a higher BMI (and a presumably higher BMD), postmenopausal women with T2DM (n=1682; mean age, 62 years) had a 1.7-fold (95% confidence interval (CI), 1.21～-2.38) higher risk for self-reported hip fractures than women without T2DM (n=30,377) in the Iowa Women's Health Study35. Data from the Rotterdam study (see details above) confirmed that patients with T2DM have an increased fracture risk despite a higher BMD36. The hazard ratio for fracture risk was 1.33 (95% CI, 1.00～
-1.76) for nonvertebral fractures. In subset analysis, the increased fracture risk appeared restricted to treated DM subjects only: HR 1.69 (1.16～2.46). The most likely explanation for these findings is that the presence of T2DM may predispose to a higher incidence of falls, because 25% of patients with treated T2DM, but only 15% of nondiabetic subjects, reported falls36. In addition, factors other than BMD and falls seem to influence fracture risk.
In a large prospective cohort study of 9249 women as part of the Study of Osteoporotic Fractures, in which the presence of diabetes mellitus was assessed by a questionnaire, 629 women (6.8%) had diabetes that was classified as noninsulin-treated diabetes (530 women) or insulin-treated diabetes mellitus (99 women)37. The majority of these women apparently suffered from T2DM. Insulin-treated women with diabetes mellitus constituted the group with the highest incidence of falls (age-adjusted OR: 2.78; 95% CI, 1.82～-4.24), followed by non–insulin- treated women with diabetes mellitus (age-adjusted OR: 1.68; 95% CI, 1.37～2.07).
This study did not assess fractures. A potential bias in this study may have been that those with more complicated T2DM may have been more likely to be switched from a diet and exercise or oral anti-diabetic
drug regimen (which combined for the noninsulin-treated group) to insulin therapy. It is also possible that hypoglycemic episodes under insulin therapy may have contributed to the increased risk for falls. Women with diabetes mellitus who reported falls commonly had multiple established risk factors, including advanced age, impaired balance, a history of coronary heart disease or arthritis, and peripheral neuropathy37. Recently, it has been reported reduced vibration perception was more likely in older women with T2DM with a history of falling. Early recognition and improved management of diabetes by reducing the incidence of neuropathy may help reduce falls. reduced vibration perception (a measure of peripheral neuro- pathy) is an important risk factor for falling and that QUS, as opposed to DXA, may be a more useful method for fracture risk prediction in older women with T2DM38.
FRACTURES AND DIABETES MELLITUS
1. T1DM and fractures
Many studies reported a trend towards increased fracture risks at most skeletal sites among patients with T1DM39-41.
Humeral fractures: Kelsey et al. (1992) determined that, in a prospective cohort of 9704 women aged 65 years or older and enrolled in the Study of Osteo- porotic Fractures, those with insulin-dependent or insulin-treated diabetes (the two terms are used synonymously by the authors) had an increased rate of fractures of the proximal humerus [relative risk (RR) 3.79; 95% CI: 1.16～12.36] compared with women without insulin-dependent diabetes42. It must be noted, however, that confusion is possible because insulin- treated diabetes does not necessarily mean type 1 diabetes. Therefore, the association between humeral fractures and type 1 diabetes is not clear.
Hip fractures: T1DM has been associated with an
increased risk of hip fractures with RRs ranging from 6.9 to 12.25. For example, Forsen et al. (1999) reported that the rate of hip fractures was significantly increased in women with T1DM, aged 50～74 years, compared with non-diabetic women of similar age (RR 6.9; 95%
CI: 2.2～21.6). The increased rate of hip fractures among diabetic men in that study was not significant43. Nicodemus et al. (2001) demonstrated that postmeno- pausal women with T1DM were 12.25 (95% CI: 5.0～
29.7) times more likely to report a hip-fracture incident than women without diabetes mellitus35. Miao et al.
also showed that, in comparison to the general population, Swedish men and women hospitalized for T1DM at least once before age 31 had increased hip-fracture risks, with standardized hospitalization ratios (SHR) of 7.6 (95% CI: 5.9～9.6) among men and 9.8 (95% CI: 7.3～12.9) among women44. The SHR is defined as the ratio of the observed to the expected numbers of first hospitalizations. Recently, in the Nurses’ Health Study cohort, Janghorbani et al.
(2006) documented that women with T1DM had a greater risk of hip fractures compared with women without diabetes mellitus (RR 7.1; 95% CI: 4.4～
11.4)45. In the meta- analysis by Vestergaard, most of the reviewed studies only assessed the association between type 1 diabetes and hip fractures13, and found a significant increase in hip fracture risk (RR 6.94;
95% CI: 3.25～14.78) associated with T1DM.
Any fractures: Adopting a case-control design, Vestergaard et al. (2005) found that T1DM was associated with an increased risk of fractures at all sites. The odds ratios (ORs) and 95% CI reported by the authors in patients with T1DM versus those with no diabetes were: any fracture 1.3, 1.2～1.5; hip fracture 1.7, 1.3～4.6; and spinal fracture 2.5, 1.3～4.6;
respectively46.
2. T2DM and fractures
T2DM has also been associated with an increased risk of fractures at any skeletal site.
Hip fractures: As in T1DM, the risk of hip fractures is increased in T2DM, although to a lesser magnitude, with risks varying from 1.5- to 2.8-fold. Forsen et al.
(1999) found a non-significant increase in the rate of hip fractures in women with T2DM, 50～74 years of age, compared with non-diabetic women in the same age group43. The crude RRs and 95% CI for these female patients were 1.8 and 1.1～2.9, respectively.
However, this increase was no longer statistically significant after adjustment for complications of diabetes such as impaired vision and motor abilities, although the point estimate remained higher than 1 (adjusted RR: 1.5; 95% CI: 0.9～2.5). In the study by Nicodemus et al., postmenopausal women with type 2 diabetes had a 1.7-fold higher risk (95% CI: 1.2～2.4) of hip fracture than women without diabetes. In addition, a longer duration of diabetes and the use of insulin or oral diabetes medications in women with T2DM were associated with a higher hip-fracture rate39. Schwartz et al. suggested that older women with T2DM had an increased risk of hip fracture (RR 1.82; 95%
CI: 1.24～2.69) in comparison to women without T2DM47. This was also demonstrated for hip fractures in older Mexican-Americans by Ottenbacher et al.
(2002) [hazard ratio (HR) 1.57; 95% CI: 1.03～2.39 for patients with diabetes versus subjects without diabetes], particularly in those with diabetes taking insulin compared with non-diabetic subjects (HR 2.84; 95%
CI: 1.49～5.43)48. Taylor et al. reported that T2DM was associated with a 68% increase in the risk of hip fractures [adjusted HR in those with T2DM versus those without T2DM 1.68 (95% CI 1.23～2.3)]49. In nursing-home patients, despite decreased bone turnover and higher bone mass among women with T2DM, hip-fracture risk was similar between women with and without diabetes. This finding could perhaps be explained by the fact that the study population was frail and had many significant risk factors for fracture that may have overwhelmed those of diabetes50.
Humeral fractures: Schwartz et al. suggested that
women with T2DM had an increased risk of proximal humerus fracture (RR 1.94; 95% CI: 1.24～3.02) in comparison to women without the disease47.
Any fractures: In the Health ABC Study, T2DM was associated with an elevated fracture risk (RR 1.64; 95%
CI: 1.07～2.5)40. In the Women's Health Initiative Study, although women with type 2 diabetes had higher BMD levels compared with women without T2DM at baseline, they had an increased risk of fractures at the seven-year follow-up (RR 1.2; 95% CI: 1.1～1.3). This trend was also evident among black women with T2DM compared with non-diabetics (RR 1.3; 95% CI:
1–1.8)41. In the Rotterdam Study, even when patients with diabetes had a higher BMD at baseline, they had an increased risk of non-vertebral fractures (HR 1.33;
95% CI: 1.00～1.77)36. In a subgroup analysis, the increased risk appeared to be restricted to diabetic patients receiving pharmacological treatment (HR 1.69;
95% CI: 1.16～2.46). The Nurses’ Health Study also revealed a slight increase in fracture risk in women with T2DM in comparison to their counterparts without the disease (RR 2.2; 95% CI: 1.8～2.7). This observa- tion was stronger among women with a longer diabetes duration compared with non-diabetic women45. Vester- gaard et al. (2005) showed that patients with T2DM, in comparison to non-type-2 diabetics, were at increased risk of: any fracture (OR 1.2; 95% CI: 1.1～1.3); hip fracture (OR 1.4; 95% CI: 1.2～1.6); and forearm frac- ture (OR 1.2; 95% CI: 1.3～4.6)46. Finally, Vester- gaard's meta-analysis revealed a significant association between diabetes and hip-fracture risk (RR 1.38; 95%
CI: 1.25～1.53). The risk of wrist fracture was also slightly increased among patients with diabetes com- pared with non-diabetic controls (RR 1.19; 95% CI 1.01～1.41). However, this was not the case for spine fractures (RR 0.93; 95% CI: 0.63～1.37). The risk of hip fracture was significantly higher in T1DM than in T2DM13.
In summary, the reviewed literature suggests an increase in fracture risks in both T1DM and T2DM.
The fracture-risk point estimates described in T1DM are considerably higher than in T2DM. It is, therefore, possible that the increased BMD in T2DM is protective against fractures, and that longstanding T2DM may increase the risk of falls and the risk of fractures, despite greater BMD. The pathophysiological expla- nations for increased fracture risks are that Skeletal factors, such as decreased BMD and poor bone quality, are addressed first, followed by the extraskeletal factors that may contribute to the increased risk of fractures in diabetes mellitus, such as the propensity to fall.
CLINICAL RECOMMENDATIONS
At present, although patients with T1DM or T2DM may be at greater risk of fractures, routine screening or initiation of preventative medications for osteoporosis is not recommended. However, bone health should be part of the evaluation of all diabetic patients. A patient- specific approach should be taken when evaluating, preventing or treating osteoporosis in diabetes mellitus.
These patients should first be evaluated according to the Canadian guidelines for the diagnosis and mana- gement of osteoporosis51 for all ‘classical’ major and minor risk factors of osteoporosis. Major risk factors include age greater or equal to 65 years, personal history of fracture as an adult, history of fragility fracture in a first-degree relative, personal history of fragility fracture after age 40, systemic glucocorticoid therapy for more than three months, malabsorption syndrome, primary hyperparathyroidism, propensity to falls, osteopenia on plain X-ray, hypogonadism and early menopause (before age 45). Minor risk factors include rheumatoid arthritis, past hyperthyroidism, chronic anticonvulsant therapy, low dietary calcium intake, low body weight (less than 57 kg), current cigarette-smoking, alcoholism, excessive caffeine intake, weight loss greater than 10% of weight at age 25 and chronic heparin therapy51. Also, retinopathy, nephro- pathy, neuropathy and vascular disease should be
verified to identify additional risk factors for low BMD and falls. It is also important to remember that patients with T1DM are at high risk of other autoimmune diseases such as celiac disease and autoimmune thyroid disease, which can contribute to low BMD.
Common sense suggests BMD screening of T1DM or T2DM patients who have any complications.
However, in T2DM, normal BMD measurements may be misleading in the assessment of fracture risk because of poor bone quality. As regards to treatment, evidence- based recommendations for osteoporosis in diabetes are not available. However, glycemic control is crucial for preventing diabetic complications and limiting bone fragility. Furthermore, according to Canadian guidelines for osteoporosis, all adults — diabetic or not — aged between 19 and 50 years should receive 1,000 mg of elemental calcium and 400 IU of vitamin D3 daily, and all those aged over 50 should take 1,500 mg of elemental calcium and 800 IU of vitamin D3 daily51. This can be achieved through a calcium- and vitamin D-adequate diet. Dietary supplements are also helpful for meeting the recommendations for calcium and vitamin D levels. Exercise should be promoted for successful weight management as well as improvements in bone and muscle mass, which are important in preventing falls. Patients with low-impact fractures or osteoporosis should be offered the same pharmaco- logical treatment as those without diabetes, including bisphosphonates, raloxifen and calcitonin as first-line treatments. It remains to be verified, however, if these drugs have the same beneficial effects in patients with diabetes as in non-diabetics.
CONCLUSION
Patients with T1DM are at greater risk of fractures because of low BMD and an increased risk of falls.
Lower BMD is explained by insulinopenia and hyper- glycemia, which impair bone formation. Furthermore, poor long-term glycemic control induces retinopathy,
neuropathy and nephropathy, which are associated with lower bone mass. In addition, retinopathy and neuro- pathy put all patients at increased risk of falls. On the other hand, patients with T2DM also have an increased risk of fractures in spite of higher BMD. The increased BMD persists even after adjustment for BMI, sugge- sting that the low bone turnover is responsible for the decreased age-related bone loss in T2DM. In these patients, the main mechanism to explain the increased risk of fractures is the propensity to falls. Thus, adequate glycemic control, and calcium and vitamin D intakes, screening for low BMD, and the prevention and treatment of diabetic complications are key elements in the elimination of osteoporosis in both types of diabetes. Patients with osteoporosis and diabetes should be offered the same pharmacological treatments as non-diabetics.
Future studies need to be prospective, and include the evaluation of bone quality, BMI, diabetes duration, falls, HbA1C, complications and BMD, to clarify the association between diabetes and fractures. Additional studies are also required to determine whether TZD (thiazolidinediones) drugs increase the risk of fractures in patients. Finally, osteoporosis trials need to include subgroups of diabetic patients with enough power to provide evidence-based guidelines for osteoporosis management in diabetes mellitus.
REFERENCES
1. Albright F, Reifenstein EC. Bone development in diabetic children; a roentgen study. Am J Med Sci 1948;174:313-9.
2. McNair P, Madsbad S, Christiansen C, Faber OK, Transbol I, Binder C. Osteopenia in insulin treated diabetes mellitus. Its relation to age at onset, sex and duration of disease. Diabetologia 1978;15:87- 90.
3. Rosenbloom AL, Lezotte DC, Weber FT, Gudat J, Heller DR, Weber ML, et al. Diminution of bone
mass in childhood diabetes. Diabetes 1977;26:1052- 5.
4. Santiago JV, McAlister WH, Ratzan SK, Bussman Y, Haymond MW, Shackelford G, et al. Decreased cortical thickness &osteopenia in children with diabetes mellitus. J Clin Endocrinol Metab 1977;45:
845-8.
5. Lopez-Ibarra PJ, Pastor MM, Escobar-Jimenez F, Pardo MD, Gonzalez AG, Luna JD, et al. Bone mineral density at time of clinical diagnosis of adult-onset type 1 diabetes mellitus. Endocr Pract 2001;7:346-51.
6. Tuominen JT, Impivaara O, Puukka P, Ronnemaa T. Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 1999;22:1196-200.
7. Heap J, Murray MA, Miller SC, Jalili T, Moyer- Mileur LJ. Alterations in bone characteristics asso- ciated with glycemic control in adolescents with type 1 diabetes mellitus. J Pediatr 2004;144:56.
8. 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.
9. Valerio G, Del Puente A, Esposito-Del Puente A, Buono P, Mozzillo E, Franzese A, The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Horm Res 2002;58:266-72.
10. Kayath MJ, Tavares EF, Dib SA, Vieira JGH.
Prospective bone mineral density evaluation in patients with insulin-dependent diabetes mellitus. J Diabetes Complications 1998;12:133.
11. Kemink SA, Hermus AR, Swinkels LM, Lutterman JA, Smals AG. Osteopenia in insulin-dependent diabetes mellitus; Prevalence and aspects of patho- physiology. J Endocrinol Invest 2000;23:295-303.
12. Munoz-Torres M, Jodar E, Escobar-Jimenez F, Lopez-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.
13. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes-a meta-analysis. Osteoporos Int 2007;18:427-44.
14. Rishaug U, Birkeland KI, Falch JA, Vaaler S.
Bone mass in non-insulin-dependent diabetes melli- tus. Scand J Clin Lab Invest 1995;55:257-62.
15. Sahin G, Bagis S, Cimen OB, Ozisik S, Guler H, Erdogan C. Lumbar and femoral bone mineral den- sity in type 2 Turkish diabetic patients. Acta Medica (Hradec Kralove) 2001;44:141-3.
16. Sert M, Tetiker T, Kirim S, Soyupak S, Cana- taroglu A, Kocak M. Type 2 diabetes mellitus and osteopenia; is there an association? Acta Diabetol 2003;40:105-8.
17. Lunt H, Florkowski CM, Cook HB, Whitehead MR. Bone mineral density, type 1 diabetes, and celiac disease. Diabetes Care 2001;24:791-2.
18. Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Zmuda JM, et al. Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study. J Bone Miner Res 2004;19:
1084-91.
19. Hampson G, Evans C, Petitt RJ, Evans WD, Woodhead SJ, Peters JR, et al. Bone mineral density, collagen type 1 alpha 1 genotypes and bone turnover in premenopausal women with dia- betes mellitus. Diabetologia 1998;41:1314-20.
20. Sosa M, Dominguez M, Navarro MC, Segarra MC, Hernandez D, de Pablos P, et al. Bone mineral metabolism is normal in non-insulin-dependent diabetes mellitus. J Diabetes Complications 1996;
10:201-05.
21. 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.
22. Majima T, Komatsu Y, Yamada T, Koike Y, Shigemoto M, Takagi C, Hatanaka I, Nakao K.
Decreased bone mineral density at the distal radius, but not at the lumbar spine or the femoral neck, in Japanese type 2 diabetic patients. Osteoporos Int 2005;16:907-13.
23. Al-Maatouq MA, El-Desouki MI, Othman SA, Mattar EH, Babay ZA, Addar M. Prevalence of osteoporosis among postmenopausal females with diabetes mellitus. Saudi Med J 2004;25:1423-7.
24. Resnick D, Shaul SR, Robins JM. Diffuse idio- pathic skeletal hyperostosis (DISH); Forestier's di- sease with extraspinal manifestations. Radiology 1975;115:513-24.
25. Rozadilla A, Nolla JM, Montana E, Fiter J, Gomez-Vaquero C, Soler J, Roig-Escofet D. Bone mineral density in patients with type 1 diabetes mellitus. Joint Bone Spine 2000;67:215-8.
26. Campos Pastor MM, Lopez-Ibarra PJ, Escobar- Jimenez F, Serrano Pardo MD, Garcia-Cervigon AG. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus; A prospective study. Osteoporos Int 2000;11:455-9.
27. 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.
28. Clausen P, Feldt-Rasmussen B, Jacobsen P, Rossing K, Parving HH, Nielsen PK, Feldt- Rasmussen U, Olgaard K. Microalbuminuria as an early indicator of osteopenia in male insulin dependent diabetic patients. Diabet Med 1997;14:
1038-43.
29. Olmos JM, Perez-Castrillon JL, Garcia MT, Garrido JC, Amado JA, Gonzalez-Macias J. Bone densitometry and biochemical bone remodeling markers in type 1 diabetes mellitus. Bone Miner 1994;26:1-8.
30. Lunt H, Florkowski CM, Cundy T, Kendall D,
Brown LJ, Elliot JR, Wells JE, Turner JG. A population-based study of bone mineral density in women with longstanding type 1 (insulin depen- dent) diabetes. Diabetes Res Clin Pract 1998;40:
31-8.
31. Ingberg CM, Palmer M, Aman J, Arvidsson B, Schvarcz E, Berne C. Body composition and bone mineral density in long-standing type 1 diabetes. J Intern Med 2004;255:392-8.
32. Wakasugi M, Wakao R, Tawata M, Gan N, Koizumi K, Onaya T. Bone mineral density measured by dual energy x-ray absorptiometry in patients with non-insulin-dependent diabetes melli- tus. Bone 1993;14:29-33.
33. Perez-Castrillon JL, De Luis D, Martin-Escudero JC, Asensio T, del Amo R, Izaola O. Non-insulin- dependent diabetes, bone mineral density, and cardiovascular risk factors. J Diabetes Complica- tions 2004;18:317-21.
34. Lenchik L, Register TC, Hsu FC, Lohman K, Nicklas BJ, Freedman BI, Langefeld CD, Carr JJ, Bowden DW. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone 2003;33:646-51.
35. Nicodemus KK, Folsom AR, Iowa Women’s Health Study. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women.
Diabetes Care 2001;24:1192–1197.
36. de Liefde II, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols HA. Bone mineral density and fracture risk in type-2 diabetes mellitus;
The Rotterdam Study. Osteoporos Int 2005;16:1713- 20.
37. Schwartz AV, Hillier TA, Sellmeyer DE, Resnick HE, Gregg E, Ensrud KE, Schreiner PJ, Margolis KL, Cauley JA, Nevitt MC, Black DM, Cummings SR. Older women with diabetes have a higher risk of falls; A prospective study. Diabetes Care 2002;
25:1749-54.
38. Patel S, Hyer S, Tweed K, Kerry S, Allan K,
Rodin A, Barron J. Risk factors for fractures and falls in older women with type 2 diabetes mellitus.
Calcif Tissue Int 2008;82:87-91.
39. Nicodemus KK, Folsom AR. Type 1 and Type 2 diabetes and incident hip fractures in postmenopau- sal women. Diabetes Care 2001;24:1192-7.
40. Strotmeyer ES, Cauley JA, Schwartz AV, Nevitt MC, Resnick HE, Bauer DC, et al. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults; the health, aging, and body composition study. Arch Intern Med 2005;165:1612-7.
41. Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, et al. Risk of fra- cture in women with type 2 diabetes; the Women's Health Initiative Observational Study. J Clin Endo- crinol Metab 2006;91:3404-10.
42. The Study of Osteoporotic Fractures Research Group, Kelsey JL, Browner WS, Seeley DG, Nevitt MC, Cummings SR. Risk factors for fractures of the distal forearm and proximal humerus. Am J Epidemiol 1992;135:477-89.
43. 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.
44. Miao J, Brismar K, Nyren O, Ugarph-Morawski A, Ye W. Elevated hip fracture risk in type 1 diabetic patients; a population-based cohort study in Swe- den. Diabetes Care 2005;28:2850-5.
45. Janghorbani M, Feskanich D, Willett WC, Hu F.
Prospective study of diabetes and risk of hip fracture; The Nurses’ Health Study. Diabetes Care 2006;29:1573-8.
46. Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medica- tion on relative fracture risk. Diabetologia 2005;48:
1292-9.
47. Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley
JA, Tabor HK, Schreiner PJ, et al. Older women with diabetes have an increased risk of fracture; a prospective study. J Clin Endocrinol Metab 2001;
86:32-8.
48. Ottenbacher KJ, Ostir GV, Peek MK, Goodwin JS, Markides KS. Diabetes mellitus as a risk factor for hip fracture in Mexican American older adults. J Gerontol A Biol Sci Med Sci 2002;57:M648-M653.
49. Taylor BC, Schreiner PJ, Stone KL, Fink HA, Cummings SR, Nevitt MC, et al. Long-term predic- tion of incident hip fracture risk in elderly white
women; study of osteoporotic fractures. J Am Geriatr Soc 2004;52:1479-86.
50. Dobnig H, Piswanger-Solkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, 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.
51. Brown JP, Josse RG. clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002;167:1S-34S.
￭ ABSTRACT ￭
Diabetes mellitus is a major risk factor for osteoporotic fractures. The occurrence of Osteoporosis among patients who have diabetes mellitus further increases both economically and physically their burden of disease.
Nevertheless, osteoporotic screening or prophylactic treatment for all patients with type 1 and type 2 diabetes mellitus is not being recommended at present. The reason is that neither the relationship between diabetes and osteoporosis and nor differences between type 1 and type 2 diabetes mellitus are clear.
At present, while low bone mineral density (BMD) is consistently observed in type 1 diabetes mellitus, the relationship is less clear for type 2 diabetes mellitus, with some studies reporting modestly increased or an unchanged BMD. Both type 1 and type 2 diabetes mellitus have been associated with a higher risk of fractures.
The presence of micro- and macro-vascular diabetic complications as a result of long standing poor glycemic control, rather than long duration predict low BMD in patients with type 1 diabetes mellitus. In type 2 diabetes mellitus patients, obesity protects bone loss and increases BMD. Nevertheless, hypoglycemic episodes under insulin therapy with commonly established risk factors of falls such as advanced age, impaired balance, a history of coronary heart disease or arthritis and peripheral neuropathy may have contributed to the increased risk for falls and result in fractures. We suggest that osteoporosis screening and prophylactic treatment for all patients with type 1 and 2 diabetes mellitus needs to be recommended along with considerations of each individual’s risk profile for osteoporotic fractures.
Key Words: Osteoporosis, Diabetes mellitus type 1 and type 2, Osteopenia, Fracture, Bone mineral density
Peer Reviewers' Commentary
이 논문은 당뇨병과 골다공증성 골절위험에 관한 내용으로, 정상인에 비해 당뇨병 환자에서 골절위험이 높기 때문에 다른 합병증과 더불어 관심을 가지고 관리할 필요성이 있다는 것을 강조하고 있다. 골밀도가 골절을 예측하는 데 가장 중요한 인자임에도 불구하고, 당뇨병 환자에서 골밀도와 골절의 연관성에 관한 연구결과는 일관성이 없다. 이는 당뇨 병이 고혈당 외에 매우 다양한 대사적 이상을 동반하는 이질적인 질환이고, 동반하고 있는 대사적 이상의 종류와 정도 가 다를 수 있으며, 이러한 이상은 골밀도뿐 아니라 골질에도 영향을 줄 수 있기 때문으로 생각하고 있다. 따라서 당 뇨병과 골다공증성 골절위험간의 연관성을 규명하기 위해서는 저자가 언급한 데로 당뇨병과 뼈 강도에 공통적으로 작용할 수 있는 다양한 요인을 찾는 전향적 연구가 필요하다. 한편, 임상적으로는 당뇨병 환자를 관리하는 데 있어 골다공증 또는 골절의 위험요인을 파악하고 골절 예방을 위한 환자교육을 하며, 적절한 시기에 선별검사와 치료를 할 수 있도록 뼈 건강에 대한 모니터링을 하는 것이 필요하다.
(정리: 편집위원회)
