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
2.
3. To download the lecture contact me
drgawad@gmail.com
For more Nephrology lectures visit
www.NephroTube.com
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
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
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)
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
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.