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1. Osteoporosis in CKD
The Challenge
Mohammed Abdel Gawad
Nephrologist
Alexandria - Egypt
NephroTube Chairman
drgawad@gmail.com
9th International Conference
Mansoura University Nephrology Unit
10-12, April, 2018

3. To download the lecture contact me
drgawad@gmail.com
For more Nephrology lectures visit
www.NephroTube.com

4. MBD
+
MVD
+
MSD
CKD - MBD

5. 2013 Nov;9(11):681-92

6. 2018;3 8(5):476–490

7. Why Diagnosis & Management of
Osteoporosis in CKD are Important?
ESRD is associated with
an increased risk of
fragility (low trauma)
fractures
The risk of fracture-
related mortality
increases with the
severity of CKD
Am J Kidney Dis. 2000;36(6):1115
Am J Kidney Dis. 2006;47(1):149
Am J Kidney Dis. 2000;36(6):1115
NDT. 2009 May;24(5):1539-44
NHANES
Osteoporos Int 14: 570–576, 2003
J Am Soc Nephrol 17: 3223–3232, 2006

8. Challenges
• Assessment of Fracture Risk & Osteoporosis in CKD
• Management of Osteoporosis in CKD

9. Challenges
• Assessment of Fracture Risk & Osteoporosis in CKD
• Management of Osteoporosis in CKD

10. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355

11. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355

12. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355

13. DEXA Scan to Assess Fracture Risk in CKD
CKD
Stage
eGFR Based on
WHO criteria
KDIGO 2009 KDIGO 2017
G1 ≥ 90 may be used may be used may be used
G2 60 - 90 may be used may be used may be used
G3 30 - 59 may be used not be performed
routinely, because it
doesn’t predict
fracture risk or
predict the type of
osteodystrophy (2B)
In patients with evidence of
CKD-MBD and/or risk factors for
osteoporosis, suggest BMD
testing to assess fracture risk if
results will impact treatment
decisions (2B)
G4 15 - 29 -----------------
G5 < 15 -----------------

14. DEXA Scan to Assess Fracture Risk in CKD
CKD
Stage
eGFR Based on
WHO criteria
KDIGO 2009 KDIGO 2017
G1 ≥ 90 may be used may be used may be used
G2 60 - 90 may be used may be used may be used
G3 30 - 59 may be used not be performed
routinely, because it
doesn’t predict
fracture risk or
predict the type of
osteodystrophy (2B)
In patients with evidence of
CKD-MBD and/or risk factors for
osteoporosis, suggest BMD
testing to assess fracture risk if
results will impact treatment
decisions (2B)
G4 15 - 29 -----------------
G5 < 15 -----------------

15. DEXA Scan to Assess Fracture Risk in CKD
CKD
Stage
eGFR Based on
WHO criteria
KDIGO 2009 KDIGO 2017
G1 ≥ 90 may be used may be used may be used
G2 60 - 90 may be used may be used may be used
G3 30 - 59 may be used not be performed
routinely, because it
doesn’t predict
fracture risk or
predict the type of
osteodystrophy (2B)
In patients with evidence of
CKD-MBD and/or risk factors for
osteoporosis, suggest BMD
testing to assess fracture risk if
results will impact treatment
decisions (2B)
G4 15 - 29 -----------------
G5 < 15 -----------------

16. DEXA Scan to Assess Fracture Risk in CKD
CKD
Stage
eGFR Based on
WHO criteria
KDIGO 2009 KDIGO 2017
G1 ≥ 90 may be used may be used may be used
G2 60 - 90 may be used may be used may be used
G3 30 - 59 may be used not be performed
routinely, because it
doesn’t predict
fracture risk or
predict the type of
osteodystrophy (2B)
In patients with evidence of
CKD-MBD and/or risk factors for
osteoporosis, suggest BMD
testing to assess fracture risk if
results will impact treatment
decisions (2B)
G4 15 - 29 -----------------
G5 < 15 -----------------

17. DEXA Scan to Assess Fracture Risk in CKD
CKD
Stage
eGFR Based on
WHO criteria
KDIGO 2009 KDIGO 2017
G1 ≥ 90 may be used may be used may be used
G2 60 - 90 may be used may be used may be used
G3 30 - 59 may be used not be performed
routinely, because it
doesn’t predict
fracture risk or
predict the type of
osteodystrophy (2B)
In patients with evidence of
CKD-MBD and/or risk factors for
osteoporosis, suggest BMD
testing to assess fracture risk if
results will impact treatment
decisions (2B)
G4 15 - 29 -----------------
G5 < 15 -----------------
Clin J Am Soc Nephrol 7: 1130–1136, 2012
Nephrol Dial Transplant 27: 345–351, 2012
J Bone Miner Res 30: 913–919, 2015
Clin J Am Soc Nephrol 10: 646–653, 2015

18. 2018 Jun 7;13(6):962-969
High bone Turnover Low bone Turnover

19. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355

20. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355

21. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355
DXA cannot distinguish
between cortical and
cancellous bone,
and it cannot assess bone
microarchitecture or bone
turnover
High-resolution peripheral
quantitative computed
tomography
Allow noninvasive, three-
dimensional evaluation of
bone microarchitecture
J Magn Reson Imaging. 2004 Jul;20(1):83-9
There are few data evaluating
these techniques in patients with
CKD, and they are not available
in most clinical settings.

22. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355
Osteoporos Int. 2009 Jun;20(6):843-51
J Am Soc Nephrol. 2011 Aug;22(8):1560-72
Osteoporos Int. 2012;23(10):2425
Osteoporos Int. 2011 Feb;22(2):391-420
Serum C-
telopeptide
(CTX)
Monomeric
forms of serum
propeptide type
I collagen (PINP)
preferred
marker of bone
resorption
preferred
markers of bone
formation

23. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355
Osteoporos Int. 2009 Jun;20(6):843-51
J Am Soc Nephrol. 2011 Aug;22(8):1560-72
Osteoporos Int. 2012;23(10):2425
Osteoporos Int. 2011 Feb;22(2):391-420
Serum C-
telopeptide
(CTX)
Monomeric
forms of serum
propeptide type
I collagen (PINP)
preferred
marker of bone
resorption
preferred
markers of bone
formation
Both cleared by
the kidney

24. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355
J Am Soc Nephrol. 2011 Aug;22(8):1560-72
Eur J Clin Pharmacol. 2006 Oct;62(10):781-92
provide better
discriminatory data
on turnover than
those cleared by the
kidney
Tartrate resistant
acid phosphatase
(TRAP5b, an
osteoclast cellular
marker)

25. Assessment of Fracture Risk in CKD
2017 Dec;92(6):1343-1355

26. https://www.sheffield.ac.uk/FRAX/
FRAX estimates the
10-year probability
of hip fracture and
major osteoporotic
fracture for
untreated patients
between ages 40 and
90 years
FRAX does not
include any
adjustment of risk
according to GFR

27. 2019 Feb;95(2):447-454
Non-dialysis CKD

28. 2019 Feb;95(2):447-454
FRAX predicted risk for major osteoporotic fracture and hip
fracture in all eGFR strata

29. Challenges
• Assessment of Fracture Risk & Osteoporosis in CKD
• Management of Osteoporosis in CKD

30. Challenges
• Assessment of Fracture Risk & Osteoporosis in CKD
• Management of Osteoporosis in CKD

31. 2018 Jun 7;13(6):962-969
High bone Turnover Low bone Turnover

32. 2018 Jun 7;13(6):962-969
High bone Turnover Low bone Turnover

33. 2018 Jun 7;13(6):962-969
High bone Turnover Low bone Turnover
Bisphosphonates /
Osteoporosis Medications ??

34. Bisphosphonates / Osteoporosis Medications
G3a–G3b
biochemical
abnormalities
of CKD-MBD
are absent)
biochemical
abnormalities
of CKD-MBD
are present
CKD G4–G5D
(Usually biochemical
abnormalities of CKD-
MBD are present)
Treatment choices take into
account the magnitude and
reversibility of biochemical
abnormalities and the
progression of CKD, with
consideration of a bone
biopsy
CKD G1–G2
(Usually biochemical
abnormalities of CKD-
MBD are absent)
Osteoporosis
management as for the
general population
If biochemical abnormalities !!
If no biochemical abnormalities !!

35. Bisphosphonates / Osteoporosis Medications
biochemical abnormalities
of CKD-MBD are present
Treatment choices take into
account the magnitude and
reversibility of biochemical
abnormalities and the
progression of CKD, with
consideration of a bone
biopsy
biochemical
abnormalities of CKD-
MBD are absent
Osteoporosis
management as for the
general population

36. Bisphosphonates / Osteoporosis Medications
biochemical abnormalities
of CKD-MBD are present
Treatment choices take into
account the magnitude and
reversibility of biochemical
abnormalities and the
progression of CKD, with
consideration of a bone
biopsy
biochemical
abnormalities of CKD-
MBD are absent
Osteoporosis
management as for the
general population

37. 2018 Jun 7;13(6):962-969
High bone Turnover Low bone Turnover
PTH <100 pg/mLPTH >350 pg/mL
PTH Level References:
Kidney Int. 2006;69(11):1945
Am J Kidney Dis. 2016 Apr;67(4):559-66
However, there are no
primary data on any of
these agents on skeletal
and extraskeletal safety
and antifracture efficacy
in patients with CKD-MBD
Ann Intern Med 166: 649–658, 2017
Although trials are needed
with fracture and
cardiovascular end points in
patients with moderate to
severe CKD before
osteoanabolic agents are
widely adapted in patients
with CKD-associated
osteoporosis

38. 2018 Jun 7;13(6):962-969

39. 2018 Jun 7;13(6):962-969
Data suggest that these agents are
safe with lower eGFR
J BoneMiner Res 20: 2105–2115, 2005
J BoneMiner Res 22: 503–508, 2007
Am J Kidney Dis 56: 57–68, 2010
J Nephrol 21: 510–516, 2008
Osteoporos Int 18: 59–68, 2007. 27: 1441–1450, 2016
Kidney Blood Press Res 33: 221–226, 2010

40. 2013 Nov;9(11):681-92
• Less potent antiresorptive agent than bisphosphonates
• Increases risk of thromboembolism
• Tested in eGFR < 45ml/min
• Tested in two small, short-term trials, G5 and G5D CKD
J Am Soc Nephrol. 2008 Jul;19(7):1430-8
Iran J Kidney Dis. 2014;8(6):461
Kidney Int. 2003;63(6):2269

41. Monitoring Therapy
DEXA Lab Biochemical markers of
bone turnover
Serial BMD measurements
are performed to assess the
clinical response to therapy
• Calcium
• Phosphorus
• 25-hydroxyvitamin D
• PTH
• Serum Cr & eGFR
should not be used to monitor
response to therapy in patients
with eGFR <30 mL/minute
J Clin Endocrinol Metab. 2002;87(4):1586
J Bone Miner Res. 2012;27(8):1627
Proc Nutr Soc. 2008;67(2):157
J Bone Miner Res. 2012 Aug;27(8):1623-6

42. Home Messages
• Fracture risk is high is CKD patients.
• DEXA scan is suggested by KDIGO for fracture risk assessment in CKD.
• Diagnose osteoporosis when T-score ≤2.5 or in presence of fragility
fracture whatever T-score.
• FRAX predicted risk for major osteoporotic fracture and hip fracture in
all eGFR strata.

43. Home Messages
• Life style interventions and CKD-MBG management are important to
decrease fracture risk.
• In absence of biochemical abnormalities of CKD-MBD; treat
osteoporosis as general population.
• In presence of biochemical abnormalities of CKD-MBD; treatment
choices take into account the magnitude and reversibility of
biochemical abnormalities and the progression of CKD.

44. Home Messages
• It is important to know the type of bone turnover before starting
osteoporosis medications.
• Bone turnover can be detected by lab markers, but bone biopsy may
be needed if diagnosis is not clear.
• In case of high turnover disease use antiresorptive agents.
• In case of low turnover disease use anabolic agents.

46. Thank You