Osteoporosis and chronic kidney disease

1. Osteoporosis and chronic kidney disease Sanjeev Patel Consultant Rheumatologist King’s College Hospital London WOAG Bones Cymru 12th July 2018Renal bone disease clinical meeting

2. Objectives • Definitions & epidemiology of OP and CKD • When does OP become CKD MBD? • Fracture risk evaluation • Managing OP and CKD MBD • Practical guidance

3. Know the audience • How many of you manage patients with: • Fragility fractures and CKD? • Fragility fractures and renal support • How many of you either have training in interpretation of or report DXA results? • How many of you use anti-osteoporotic treatments in patients with CKD stage 4 and 5

4. Chronic Kidney Disease-Definitions Kidney damage is defined as pathological abnormalities or markers of damage including abnormalities of urine results or on imaging , http://www.renal.org/eGFR/ckdstages.html

5. Prognosis of CKD • CKD is defined as abnormalities of kidney structure or function that are present for >3 months and have health implications. by stage and albuminuria • CKD is classified on the basis of cause, GFR category (G1 to G5), and albuminuria category (A1 to A3). • Green means low risk (no CKD if no other markers of kidney disease), yellow means moderately increased risk, orange means high risk, and red means very high risk. KDIGO 2017

6. eGFR MDRD formula Cockroft Gault formula Only an estimate. A significant error is possible. eGFR is most likely to be inaccurate in people at extremes of body type, for example malnourished, amputees, etc. Confidence intervals: 90% confidence intervals are quite wide, e.g. 90% of patients will have a measured GFR within 30% of their estimated GFR. 98% have measured values within 50% of the estimated value. Race: Some racial groups may not fit the MDRD equation well. Age Creatinine Gender Race Age Creatinine Gender Mass

7. Osteoporosis, CKD and ageing • Both osteoporosis and CKD are more prevalent with ageing • NHANES III study from USA • Examined prevalence of OP and GFR in a population based sample of US subjects Klawansky et al OI 2003;14:570-576

8. Relationship between GFR & BMD Klawansky et al OI 2003;14:570-576

9. Relationship between GFR & BMD Klawansky et al OI 2003;14:570-576

10. GFR in women with a hip fracture • US study of 100 women with hip fracture • Mean age 84 yrs (SD 9) • 76 % had GFR < 60 ml/min • 58% had GFR < 35 ml/min (CKD 3, 4 and 5) • 10% had GFR < 20 ml / min (CKD 4 and 5) Casey et al JAGS 2003;51:S166

11. GFR in patients with non-hip peripheral low trauma fracture • 736 patients over a 12 months • Outpatient management in Nottingham • Mean age 69 (range 50 to 80) 90 % female % Stavroulopoulos et al NDT 2008;23:2710-2711

12. Fracture rate and mortality after hip fracture Fully adjusted (13 categories) Recruitment 1995 to 1998 N= 14 177 Median age 80.3 yrs Baseline eGFR Follow-up until 2005 Nitsch et al NDT 2009;24:1539-1544

13. GFR and fractures • GFR is low in patients with osteoporotic fractures (by virtue of age) • Low GFR is associated with higher incidence of fractures and mortality after fracture • Mechanisms • Increased incidence of falling • Bone strength

14. 73 yr old woman with recent fragility fracture

15. 73 yr old woman with recent fragility fracture

16. 73 yr old woman with recent fragility fracture

17. 73 yr old woman with recent fragility fracture

18. Objectives • Definitions & epidemiology of OP and CKD • When does OP become CKD MBD? • Fracture risk evaluation • Managing OP and CKD MBD • Practical guidance

19. Variables determining bone strength • Bone density • Bone turnover • Bone architecture • Bone mineralisation • Bone cell apoptosis • Bone size • Bone geometry

20. Changes in bone resulting in osteoporosis

22. Variables determining bone strength in postmenopausal osteoporosis • Bone density • Bone turnover • Bone architecture • Bone mineralisation • Bone cell apoptosis • Bone size • Bone geometry

23. Bone strength and GFR • CKD causes reduction in bone strength • Complex multifactorial mechanisms • Reduced 1,25D and 25D • Low normal calcium and raised phosphate • Increased PTH and bone turnover • Abnormal mineralisation

24. CK MBD • CKD-MBD is defined as a systemic disorder of mineral and bone metabolism due to CKD, manifested by either one or a combination of the following three components: • Abnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism • Abnormalities in bone turnover, mineralization, volume linear growth, or strength (ROD) • Extraskeletal calcification

25. CKD BMD – vascular calcification

26. Variables determining bone strength in CKD MBD • Bone density • Bone turnover • Bone architecture • Bone mineralisation • Bone cell apoptosis • Bone size • Bone geometry

27. CKD and hyperparathyroidism

28. CKD and hyperparathyroidism Renal Failure

29. CKD and hyperparathyroidism Renal Failure

30. CKD and hyperparathyroidism Renal Failure

31. CKD and hyperparathyroidism Renal Failure Point of no return Fukagawa et al KI 2006

32. CKD and hyperparathyroidism Renal Failure Point of no return Fukagawa et al KI 2006 calcitriol calcimimetic Surgical parathyroidectomy

33. CKD stages, vitamin D metabolites, PTH and markers of bone turnover Multiple units N = 141 patients (not taking vitamin D) Patel et al 2008 Patel et al JBMM 2011

34. CKD stages, vitamin D metabolites, PTH and markers of bone turnover Multiple units N = 141 patients (not taking vitamin D) Patel et al 2008

35. CKD stages, vitamin D metabolites, PTH and markers of bone turnover • Multiple units N = 141 patients (not taking vitamin D) [CTX data x3 to fit scale] Patel et al 2008

36. CKD stages, vitamin D metabolites, PTH and markers of bone turnover • Multiple units DURATION N = 141 patients (not taking vitamin D) [CTX data x3 to fit scale] Patel et al 2008

37. TMV classification of bone histomorphometry in renal bone disease OM=osteomalacia AD adynamic bone disease HPT=hyperarathyroidism MUO=mixed uraemic osteodsytrophy OF=osteitis fibrosa Moe et al Kidney International (2006) 69, 1945–1953

38. Normal OFC Osteomalacia Mixed

39. Postmenopausal osteoporosis versus CKD MBD

40. Postmenopausal osteoporosis versus CKD MBD Used for the diagnosis and monitoring of CKD MBD

41. Pathogenesis of osteoporotic fractures Neuromuscular function Environmental hazards Time spent at risk Risk of fall Force of impact Strength of bone Type of fall Protective responses Energy absorption Risk of fracture Bone mineral density Geometry of bone Quality of bone

42. Pathogenesis of osteoporotic fractures Superimposed kidney related factors such as cause of CKD e.g. DM, Inflammatory conditions, glcucocorticoids Neuromuscular function Environmental hazards Time spent at risk Risk of fall Force of impact Strength of bone Type of fall Protective responses Energy absorption Risk of fracture Bone mineral density Geometry of bone Quality of bone

43. 73 yr old woman with recent fragility fracture

44. 73 yr old woman with recent fragility fracture

45. 73 yr old woman with recent fragility fracture

46. 73 yr old woman with recent fragility fracture FRACTURE RISK EVALUATIONMANAGING OP AND CKD MBDPRACTICAL GUIDANCE

47. Objectives • Definitions & epidemiology of OP and CKD • When does OP become CKD MBD? • Fracture risk evaluation • Managing OP and CKD MBD • Practical guidance

48. Fracture risk evaluation • DXA to predict fractures • SOF mean CrCl 64 ml/min (range 34 to 94) • Spinal BMD and aortic calcification Cummings et al Lancet 1995 • FRAX • Can be used in CKD stages 1 to 3 • Uncertain in CKD stages 4 to 5 • In part because CKD MBD is predominant • ? Tick secondary causes

49. Fractures, Fracture Risk and GFR Derived from Fried et al J Am Soc Neph 2007;18:282-286and Sherrard et al KI 2000;58:396-399

50. Objectives • Definitions & epidemiology of OP and CKD • When does OP become CKD MBD? • Fracture risk evaluation • Managing OP and CKD MBD • Practical guidance