Friday, March 21, 2014

Diabetes and Fracture Risk


Your skeletal health is only as deep as its microarchitecture. With almost 50% of women and 20% of men predicted to sustain an osteoporosis-related fracture in their lifetime, the possibility of fragile bones is always something everyone should be aware of. With the diabetic individual, he or she will need to take extra vigilance as they have greater fracture risk.

Diabetes has reached epidemic proportions in the United States. Over 25% of adults have diabetes and this population—especially that developing type 2 diabetes (T2D)—is growing. With medical advances, people with type 1 diabetes (T1D) are living longer and into an age where osteoporosis becomes of greater concern.

How much greater is the fracture risk for diabetic individuals?
Compared to non-diabetic individuals, the bone mineral density (BMD) of type 1 diabetic patients is only slightly lower on average than non-diabetic individuals, so one might expect only a slightly higher fracture risk. But the risk level is much greater: individuals with T1D are 12 times more likely to fracture a hip according to data from the Iowa Women’s Study.1

In contrast to T1D, individuals with T2D are often overweight and have higher than average BMD. With higher weight and increased bone density one would expect lower fracture risk. But T2D also carries an increase in fracture risk: 40% to 70% increase in risk for hip fracture and over 20% increased risk for all fractures.

It is clear that both T1D and T2D carry increased risk for spinal and hip fractures, yet BMD T scores and FRAX analysis underestimate their fracture risk. The bottom line: middle-aged and elderly diabetics are suffering a decrease in bone strength that is not measurable by current methods. Diabetes-related fracture risk is linked to reduced microarchitectural bone quality. Of course, an increase in falls due to hypoglycemic episodes, poor balance from diabetic neuropathy, and retinopathy-induced visual impairment may also be factors.

Why is the bone quality of diabetic individuals so poor?
Diabetes may affect bone in a number of ways:

1.     Chronic elevations in blood glucose weakens skeletal microarchitecture through the formation of advanced glycation end-products (AGEs) (such as carboxy-methyl-lysine and pentosidine) in both the bone-matrix collagen and the non-collagenous protein, osteocalcin2.  This non-enzymatic glycation is a spontaneous reaction that lowers bone biomechanical competence. AGE induced collagen cross-links between reducing sugars and proteins stiffen collagen, making bone less pliable and less resistant to fracture.
2.     Hyperglycemia affects bone cells leading to low bone turnover osteoporosis.
3.     Reduced osteocyte function and higher sclerostin levels may inhibit bone formation by osteoblasts.3
4.     Reduced osteoblast bone formation and increased cortical porosity may explain accelerated bone loss at the hip in T2D.
5.     A reduction in trabecular microarchitectural quality as assessed through trabecular bone score (TBS) has been implicated as contributing to the increased fracture risk in T2D despite a higher than average BMD.4
6.     Altered bone marrow fat composition (higher saturated fat) is linked to fragility fractures and diabetes.5 Excessive marrow fat leads to reduced hematopoetic stem cells and increased adipocytokine production. This lowers bone turnover rate and allows for the development of “old bone” weakened by the accumulation of microfractures.
7.     Diabetes leads to lower “insulin-like growth factor 1” production. IGF-1 is a powerful natural anabolic peptide that stimulates both muscle and bone growth.
8.     The pharmacological treatment of T2D with thiazolidinediones (PPAR gamma agonists) promotes marrow stem cell differentiation into adipocytes rather than osteoblasts.

The typical medical approach to the treatment of T2D often includes medications. Although not all diabetes medications increase fracture risk, the thiazolidinediones (rosiglitazone and pioglitazone) can double the fracture risk of women (not men) with osteoporosis. These PPAR (peroxisome proliferator activator receptor) agonist medications stimulate adipogenisis in bone marrow and reduce bone formation.

Bisphosphonates are the current medications of choice for treating osteoporosis; they work by subduing osteoclast bone resorption and slowing overall bone remodeling (including bone formation) activity. The medical community has expressed concern about using bisphosphonate drugs to treat osteoporotic T2D’s patients because a further reduction in bone formation (bisphosphonates reduce both resorption and formation activity) through the use of bisphosphonate medications in the already bone-formation suppressed microenvironment of the type 2 diabetic, could increase bone fragility even further. This seems highly likely especially with atypical femur fractures already linked to long-term bisphosphonate use in non-diabetic individuals.

If you are diabetic, talk with your doctor about things you can do to improve your blood glucose levels naturally: 

·       Diet – You will benefit from a lower carbohydrate intake and increased quality protein, healthy fats, and vegetable intake.
·       Exercise – Try to exercise 45 minutes to an hour, five days a week, and reduce stress.
·       Supplementation – Talk to your doctor or nutritionist about what specific nutrients and therapeutic compounds you can take that work synergistically to decrease insulin resistance, lower inflammation, balance blood lipids, and improve liver function, while controlling their glucose levels and preventing glycation-induced damage. The following are some of the key components to consider using if you are diabetic: activated B-complex vitamins; vitamin D3; essential minerals (especially magnesium, zinc, chromium, and vanadium) and trace minerals; antiglycating agents such as alpha lipoic acid, L-Taurine, L-Carnosine and benfotiamine; herbal support including green tea extract (EGCG) and Gymnema sylvestre leaf extract.
·       Tracking – Make sure your blood glucose and hemoglobin A1C levels are monitored. Hb A1C levels above 7% are correlated with increased fracture risk. The American Diabetic Association (ADA) recommends that people with diabetes have the Hb A1C tested every 3 to 6 months depending upon glycemic control.

In addition to lowering your fracture risk, these strategies will also help lower your risk of diabetic-related comorbidity. Hypertension, coronary and peripheral artery disease, stroke, and even spinal degeneration are all common comorbidities of diabetes.

Current medical therapy for the diabetic osteoporotic patient is problematic and a more natural, conservative, approach using diet, supplements, and exercise can substantially improve the long-term outcome. If you are diabetic, you can reduce your risk of fractures and improve your over-all health by following the simple suggestions outlined above.

 
1  Nicodemus, K.K. and A.R. Folsom. 2001. Iowa Women’s Health Study. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24:1192-1197.

2  Sroga, G. and Vashishth, D. 2013. Glycated osteocalcin. ASBMR Symposium: Cutting Edge Discoveries in Muscle Biology, Disease and Therapeutics. ASBMR Annual Meeting: Oct 4-7. P024

3  Kim, J.Y., et al. 2013. Extendin-4 increases bone mineral density in type 2 diabetes OLETF rats potentially through the down-regulation of SOST/sclerostin in osteocytes. Life Sciences Mar 21;92(10):533-40.

4  Dhaliwal, R., J. Spadaro, C. Ghosh, J. Kelly, and A. Moses. 2013. ASBMR Symposium: Cutting Edge Discoveries in Muscle Biology, Disease and Therapeutics. ASBMR Annual Meeting: Oct 4-7. SA0304

5  Patsch, J.M., et al. 2013. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res Aug;28(8):1721-8.
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