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Osteovigilance In Diabetes (Bone Health In Diabetes)

Osteovigilance In Diabetes (Bone Health In Diabetes). Dr Ameya Joshi, MD,DM(Endocrinology) Consultant endocrinologist, Bhaktivedanta Hospital And Research Institute, Endocrine And Diabetes Clinic, Mumbai Member of Executive committee of ISBMR. ONE OF MY HATS.

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Osteovigilance In Diabetes (Bone Health In Diabetes)

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  1. Osteovigilance In Diabetes (Bone Health In Diabetes) Dr Ameya Joshi, MD,DM(Endocrinology) Consultant endocrinologist, Bhaktivedanta Hospital And Research Institute, Endocrine And Diabetes Clinic, Mumbai Member of Executive committee of ISBMR

  2. ONE OF MY HATS • MEMBER AND CHAIRMAN SERIOUS ADVERSE EVENTS SUBCOMITTEE OF INSTITUTIONAL ETHICS COMITTEE VIGILANCE:TO KEEP CAREFUL WATCH FOR POSSIBLE DANGERS AND DIFFICULTIES

  3. CASE • 55/F • T2DM SINCE 20 YEARS • C/O OCC ACHES AND PAINS • BMI-34 KG/M2, BP-150/90 • DSPN +, MACROALBUMIN + • ON METFORMIN ,GLICLAZIDE, TENELIGLIPTIN AND CANAGLIFLOZIN • AN INCIDENTALLY NOTED BMD SHOWS A T SCORE 0F -2.0 AT L-SPINE

  4. WHO CLASSIFICATION: T SCORES

  5. OSTEOPOROSIS(T SCORE BELOW -2.5 ON DXA) • A disease characterized by • 1. low bone mass and • 2. micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk

  6. Diabetic complications Diabetic complications Acute (Short term) Chronic (Long term) • Hypoglycaemia • Diabetic Ketoacidosis • Hyperglycaemic Hyperosmolar Syndrome Microvascular Macrovascular • Neuropathy • Nephropathy • Retinopathy • Cardiovascular disease • Cerebrovascular disease • Peripheral vascular disease

  7. WHERE DOES BONE DISEASE STAND?

  8. Advanced GlycationEndproducts • Accumulate with age and hyperglycemia • Increase brittleness • Slow bone turnover Decrease bone strength independent of BMD

  9. AGEs Are Associated With Fractures • 765 postmenopausal women followed for 5 years; HR for 1 SD increase in urinary pentosidine 1.18 for vertebral fracture and 1.20 for long bone and vertebral fracture.Tanaka J Bone Miner Res 2011 • 76 T2D women had higher serum pentosidine levels if they had vertebral fracture (OR 2.50, CI: 1.09-5.73).Yamamoto J Clin Endocrinol Metab 2008 • Health ABC: 1,000 patients followed for 7.5 years, urinary pentosidine was associated with increased clinical fracture incidence in T2D (RH 1.42, 1.10-1.83).Schwartz J Clin Endocrinol Metab 2009 ADVERSE BONE HEALTH AND FRACTURE RISK CORRELATES WITH PRESENCE OF MICROVASCULAR DISEASE IN DIABETES Pentosidine Findings were independent of BMD

  10. Women with diabetes have higher BMD at all sites but lower TBS • 29,407 women ≥ 50 years from Manitoba • 2,356 (8.1%) had diabetes mellitus TBS and BMD (g/cm2) # * * # Adjusted for age, BMI, glucocorticoids, prior major fracture, rheumatoid arthritis, COPD as a smoking proxy, alcohol abuse, and osteoporosis therapy * * * p<0.001 Similar results if BMI < or > 30 kg/m2 Diabetes definition: separate physician claims for diabetes, or a hospitalization with a diabetes diagnosis Leslie et al, J ClinEndocrinolMetab, 2013

  11. TBS Proposed Position(from the ISCD Position Development ConferenceMarch, 2015) • TBS can be used to assess fracture risk in postmenopausal women with diabetes

  12. ENDOCRINE BONE INSULTS IN T2DM LOW VIT D HYPOGONADISM LOW IGF-1 CKD AND ITS OFFSHOOTS HYPERCORTISOLISM

  13. Sclerostin, a product of the osteocyte, inhibits bone formation Mesenchymal Stem Cell (MSC) CFU-M colony forming unit macrophage Osteoprogenitor Cell Pre-Fusion Osteoclast Pre-Osteoblast Multinucleated Osteoclast Sclerostin Osteoblast Activated Osteoclast Bone Osteocyte

  14. AND MORE TO MUSCLE….

  15. Skeletal Abnormalities in T2DM • Reduced Turnover • Abnormal Biomechanics • Reduced Bone Quality

  16. Type 2 Diabetes and Fracture Risk Meta-analyses • Vestergaard et al. 2007 (8 Studies) • Age-adjusted • By BMD alone, the RR would be expected to be lower, approximately 0.77 • But RR for hip fracture is higher, 1.38 (1.25-1.53) • Janghorbani et al.2007 (8 Studies) • Adjusted for multivariables • Hip fracture RR=1.7 (1.3-2.2) • Any fracture RR=1.2 (1.01-1.5)

  17. BMD PREDICTS FRACTURE RISK IN DIABETES:BUT RELATIONSHIP IS DIFFERENT

  18. Does FRAX Also Predict Fracture in T2D? For a given FRAX score, fracture risk is higher than predicted in T2D

  19. THERE IS SOMETHING MORE IN THE STORY Contributing Factors: • Falls? • TZDs/SGLT-2 i? • Metabolic derangements • Skeletal abnormalities? • Fat?

  20. WHY FALLS…..? • Peripheral neuropathy (impaired balance, gait) • Poorer Vision (Retinopathy) • Knee and hip osteoarthritis • Cardiovascular (CHF and arrhythmias) • History of CVA • Hypoglycemia (with insulin use) • Low vitamin D

  21. TZDs Influence The Lineage Pathway Of Marrow Mesencymal Progenitors TZDs are likely to shift bipotential bone marrow precursor cells from the osteoblast lineage tract to the adipocyte lineage tract

  22. TZDs and Fracture DON’T BLAME TZD FOR ALL AS DIABETES AS RISK FOR FRACTURE WAS KNOWN PRIOR TO THEM TZDs should not be used in women at higher risk of fracture Kahn Diabetes Care 2008

  23. CANVAS ALERTED US……BUT REST IS REASSURING

  24. OBESEITY:GOOD OR BAD? FAT IS GOOD FOR BONE OH NO….ITS BAD…. Fat can induce an artifact of the DXA measurement giving a falsely elevated BMD Co-morbidities such as diabetes and vitamin D deficiency are often present In women, an earlier menopause; in men lower testosterone levels Marrow has more fat; fewer osteoblasts Increased incidence of falls! • Low weight is a risk factor for osteoporosis/fractures • Higher weight has been associated with higher BMD and lower fracture rates • Fat is a source of estrogens (good for bones) • Higher insulin levels may be a positive skeletal factor • The extra padding of fat helps to lessen the impact of a fall!

  25. Low body weight and high body weight may both be risk factors for fracture

  26. Bariatric Surgery And Bone

  27. TYPE 1 DIABETES AND OSTEOPOROSIS: MORE OR LESS ACCEPTED AS CAUSE OF OSTEOPOROSIS

  28. FACTORS ASSOCIATED WITH FOR LOW BMD IN T1DM 1.CONCOMITTENT CELIAC DISEASE 2.INSULIN DEFICIENCY 3.POOR GLYCAEMIC CONTROL 4.LOW IGF-1 AND IGF BP3 LEVELS 5.VITAMIN D DEFICIENCY 6.ASSOCIATED HYPOGONADISM 7.ASSOCIATED RENAL FAILURE 8.EARLY AGE OF ONSET

  29. PREVIOUS STUDIES/METAANALYSIS

  30. AACE OSTEOPOROSIS GUIDELINES 2017

  31. Summary: Skeletal health in T2DM • Fracture risk is greater after accounting for BMD/FRAX • Contributing factors include falls, obesity, TZDs, SGLT-2i? And most importantly T2DM worsening bone quality • Intensive glycemic control does not increase fractures Poor control may increase fracture risk. • Standard guidelines for fracture prevention:fall prevention, nutritional adequacy and lifestyle modification should be followed • If fracture has occurred or if fracture risk is high, pharmacological treatment is appropriate, but current therapies have not been well studied

  32. GOOD CLINICAL PRACTICES • Including bone density as a part of evaluation of type 2 diabetics in postmenopausal females, males above 45 years and T1DM at risk • Considering diabetes as an important factor while making treatment decisions for osteoporosis management • Fracture prevention emphasized in diabetics with osteopenia/osteoporosis and neuropathy • Bone friendly diabetes therapeutics • Vit D repletion

  33. ABC and BEYOND • Abstinence from tobacco: excess alcohol, caffeine • Behavour & lifestyle, active • Calcium • D, Vitamin • Exercise, weight-bearing/ low impact • Fall prevention • Good nutrition • Heliophilia

  34. THANK YOU FOR LISTENING • www.isbmr.org

  35. WHAT ABOUT T2DM?

  36. TYPE 2 DIABETES • Is not listed as a risk factor of osteoporosis • Because the conventional DXA actually reads the BMD as high than normal in T2DM(5% more than controls) –the T score are 0.3-0.8 higher in diabetics –Bond, JCEM 2006 • Contrary to expectations fracture risk is higher • Hip 1.41 • Foot 1.44 • Upper arm 1.30 • Ankle 1.34 • Spine 1.28

  37. Skeletal Geometry is Worse in T2D • By BMD: femoral neck aBMD is higher, but femoral neck strength is lower relative to load Ishii J Clin Endocrinol Metab 2012 • By QCT: Trabecular BMD is higher but load to strength ratio for hip fracture is not enhanced Melton J Clin Endocrinol Metab 2008 • By pQCT: Cross sectional area and bone bending strength at cortical sites are lower Petit J Bone Miner Res 2010 Despite higher areal BMD, biomechanical indices are worse

  38. HRPQCT:Is Microarchitecture Abnormal in T2D? 82 microns High Resolution Peripheral Quantitative Computed Tomography

  39. Bottom Lines • Diabetes is bad for bones! • Obesity is bad for bones! • Diabetes AND obesity are doubly bad for bones!

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