Fractue in hd prof ahmed hassan

Fracture In Hemodialysis
Dr. Ahmed Hassan Mohamed MD
Ass.Prof.Of Nephrology
National Institute Of Urology & Nephrology
CNE
ESNT-CNE 5th Course, Cairo May 14-17, 2014

National Institute of Urology &
Nephrology (NIUN)

 Fractures are an important public health concern
associated with morbidity, mortality, and costs among
patients with ESRD.
 Compared with the general population, dialysis patients
are at an increased risk of any fracture and are 4.4–14
times more likely to experience a hip fracture.
Anne C. Beaubrun,* Ryan D. Kilpatrick,† Janet K. Freburger,‡ Brian D. Bradbury, Lily Wang,‡ and M.
Alan Brookhart|:Temporal Trends in Fracture Rates and Post discharge Outcomes among
Hemodialysis Patients., J Am Soc Nephrol 24: 1461–1469, 2013.
Introduction

Adjusted fracture incidence rates
remained constant in the years
2000–2009. Rates were highest for
pelvis/hip, vertebral, and lower leg
fracture categories. All trend lines
were adjusted for age, race, sex,
cause of ESRD & years on dialysis.
(A)Inpatient outpatient fractures.
(B) Inpatient fractures only.
A
B

 These include:
 A high prevalence of polypharmacy
 Co morbidity burden
 Decreased muscle strength
 Increased susceptibility to falls
 Secondary hyperparathyroidism and renal osteodystrophy
Anne C. Beaubrun,* Ryan D. Kilpatrick,† Janet K. Freburger,‡ Brian D. Bradbury, Lily Wang,‡ and M.
Alan Brookhart|:Temporal Trends in Fracture Rates and Postdischarge Outcomes among
Hemodialysis Patients., J Am Soc Nephrol 24: 1461–1469, 2013.
Risk factors

Drugs That Reduce Bone
Mineral Density
Mazziotti G, Canalis E, Giustina A. Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med. 2010;123:877-884.

 It composed of a number of histologically different
conditions affect patients with CKD. These include :
 Low bone turn over (a dynamic bone disease).
 High (osteitis fibrosa) bone turnover states
 Conditions of altered mineralization
All above, decrease bone strength and predispose the
patient to pathological fractures.
Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, et al. Incidence and risk factors for
hip or other bone fractures among hemodialysis patients in the Dialysis outcomes and Practice Patterns
Study. Kidney Int 2006;70:1358-66.
Renal Osteodystrophy

 B2-microglobulin related amyloidosis are a destructive
arthropathy of peripheral joints, spine, carpal tunnel
syndrome, and lytic bone lesions.
 The three main sites of lytic lesions are femoral neck,
scaphoid bone, and C1-C2 vertebra.
 An accurate diagnosis is based on bone histopathology
that must be performed, in a suspected long-term
hemodialysis patients.
Stanislas Bataille.,Carla Fernandez1. Jean-Vincent Zink., Philippe Brunet., Yvon Berland1,2and
Ste´phane Burtey,.,The Case A hip fracture in a hemodialysis patient Kidney International (2013)
83, 1211–1212
Amyloidosis

Renal Bone Diseases

Bone Structure

Bone Remodeling Cycle

Uraemic Bone RemodelingCycle
Retards:
 Vit D3
 Age
 Diabetes
 Al3+
 PTH
 TGF beta
Accelerates:
 PO4
 Ca2+,
 Vit D3
 Oestrogen
 Acidosis
 IL1,6
 TNF

Chronic Kidney Disease-MBD
Moe S, et al. Kidney Int. 2006;69:1945-1953
Laboratory:
FGF23, Ph & PTH
Calcium & calcitriol
Abnormal bone histology:
▫ Decrease BMD
▫ Mineralization
▫ Turnover
▫ Volume
Calcification:
• Soft tissue
• Coronary &valvular
• calciphylaxis

Prevalence Of Types Of Bone Disease As
Determined By Bone Biopsy

 Excess PTH
 Bone turnover activity (greater number of osteoclasts
and osteoblasts) & defective mineralization.
 Bone pain
 Increased risk of fractures.
High Turn Over Bone Disease

Emanuel Zitt on 23 May 2014.
Pathogenesis
Of
Secondary
Hyperparathyroidism.

●Low osteoblastic & osteoclastic activity  low bone
matrix synthesis
●---- of the parathyroid gland
●A low s. iPTH concentration + an elevated s. ca level.
Kevin J. Martin andEsther A. González, Disease in Chronic Kidney Disease JASN
March 8: 875-885; published ahead of print January 24, 2007, doi:10.1681
Low Turn Over Bone Disease

The factors involved in the pathogenesis of
adynamic bone in chronic kidney disease.
BFR= Bone formation rate, OPG= Osteoprotegerin, VDR = Vit.D receptors

 Disorder of mineralisation of newly formed bone matrix
 Vitamin D deficiency
 Hypophosphatemia (Fanconi syndrome, X-linked
hypophosphatemic rickets)
 Aluminium
 X-ray – Looser’s zones
 Laboratory: PO4-, vitamin D, Ca2+ &
alkaline phosphatase.
Osteomalacia

 Impairment in bone strength predisposing a person to an
increased risk of fracture. Bone strength primarily
reflects the integration of bone density and bone quality.”
 World Health Organization diagnostic criteria, based on
bone mineral density T scores:
Osteoporosis

Diagnostic Criteria For
Osteoporosis

 Asymptomatic
 Symptoms appear only late in its course including:
 Pain and stiffness in joints,
 Spontaneous tendon rupture,
 Predisposition to fracture
 Proximal muscle weakness.
Kevin J. Martin andEsther A. González, Disease in Chronic Kidney Disease
JASN March 2007 18: 875-885; published ahead of print January 24, 2007, doi:10.1681
Manifestation

 Involving the vasculature, and calcification of the skin and
calciphylaxisalsomaybeseen.
 Alteration of fetuin (inhibit soft tissue calcification) & Gla protein
(inhibit vacular calcification)  facilitate calcification from
(transformation of vascular smooth muscle cells into
osteo/chondrocytic-likecells).
Kevin J. Martin andEsther A. González, Disease in Chronic Kidney Disease JASN March 2007 18: 875-
885; published ahead of print January 24, 2007, doi:10.1681
Extraskeletal

Violaceus & Black Leathery Like Lesion
Describe Calciphylaxis In ESRD Patient.

Aluminium related disorders

Diagnosis

 Bone density measurements using dual-energy x-ray
absorptiometry (DXA):
 Measure density of the bone but not quality (cortical &
trabecular microrchitectures)
 Do not reliably differentiate between patients with or without
fractures.
 It has a lower discriminatory power for trabecular density.
Daniel Cejka, Janina M. Patsch, Michael Weber, Danielle Diarra, Markus Riegersperger, Zeljko
Kikic, Christian Krestan, Claudia Schueller-Weidekamm, Franz Kainberger, Martin Haas, Bone
Microarchitecture in Hemodialysis Patients Assessed by HR-Pqct. CJASN September 2011 vol. 6 no.
9 2264-2271
Diagnosis

 High-resolution peripheral quantitative computed
tomography (HR-pQCT):
 Measured trabecular density (determined cortical & trabecular
micro architectures).
 The strongest determinant of fracture.
DanielCejka,JaninaM.Patsch,MichaelWeber,DanielleDiarra,MarkusRiegersperger,ZeljkoKikic,ChristianKrestan,Claudia
Schueller-Weidekamm,FranzKainberger,MartinHaas,BoneMicroarchitectureinHemodialysisPatientsAssessedbyHR-Pqct.
JASNSeptember2011vol.6no.92264-2271
Diagnosis

• Bone biopsy is a gold standard in patients with CKD
stages 3-5D, it is reasonable to perform a bone biopsy in
various settings including:
▫ Unexplained fractures, hypocalcaemia &hypophosphatemia,
▫ Persistent bone pain
▫ Possible aluminum toxicity
▫ Prior to therapy with bisphosphonates in patients with CKD-
MBD
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl.2009 (113)
:S1-130.
Diagnosis

Bonebiopsies.stainedwithtartrate-resistantacidphosphatase(TRAP)
forosteoclasts.LeftpanelOriginal showsnoosteoclasts. Rightpanel
showsveryfewosteoclastsinHowship'slacunae.

Calcifiedsupportingstructuresarereplacedwithfibroustissue
(peritrabecularfibrosis),andtheformationofcyst-likebrowntumors
inandaroundthebone(Goldnertrichromestain)

 A lateral abdominal radiograph can be used to detect the
presence or absence of vascular calcification.
 An echocardiogram can be used to detect the presence or
absence of valvular calcification.
 Electron beam computed tomography to detect the
presence or absence of soft tissue calcification.
.
National kidney foundation K/DOQI clinical practice guidelines, Evaluation
and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-
MBD) 2010
Diagnosis of CKD-MBD, Vascular
Calcification

EBCT Scans Reveals Coronary Artery &
valular calcification in a Dialysis Patient.

 Tests for neuromuscular function:
(TUG and 6MW):
 Able to discriminate fracture status in patients with
Stages 3–5 CKD.
 Do not require specialized expertise/equipment
 An inexpensive method to assess for the presence of
fractures.
Conclusion

 a T score of −2.5 or lower or fragility fractures, as in the
postmenopausal population
 there are no biochemical abnormalities that suggest
chronic kidney disease–mineral and bone disorder.
Moe S, Drueke T, Cunningham J, et al.Definition, evaluation, and classification of
renaosteodystrophy: aposition statement from Kidney Disease: Improving global Outcomes
(KDIGO). Kidney Int 2006; 69:1945–1953
Diagnosis Of Osteoporosis In Patients With
Stage 1, 2, Or 3 Chronic Kidney Disease

 No universally accepted criteria.
 The diagnosis is best suggested by excluding other forms
of renal osteodystrophy by quantitative histomor-
phometry & other non invasive technique.
 Use biochemical markers before bone biopsy to
distinguish the form of renal osteodystrophy.
Diagnosis Of Osteoporosis In Patients
With Stage 5 Chronic Kidney Disease

K/DOQI clinical practice guidelines
on bone metabolism target levels
CRF stage 5
on dialysis
CRF stage 4
CRF Stage 3
3.5-5.5
2.7-4.6
2.7-4.6
Phosphorus
mg/dl
8.4- 9.5
Hyperca>10.2
Normal
Normal
Calcium
md/dl
150-300
70-110
35-70
iPTH pg/ml

 Dietary phosphate restriction
 Dialysis
 Phosphate binders:
 Aluminium-based
 Calcium-based
 NonCa2+/Al
Kevin J. Martinand , Esther A. González : Metabolic Bone Disease in Chronic Kidney Disease
JASN March 2007 vol. 18 no. 3 875-885
Management of hyperphosphatemia

 Compliance: 800 - 1000 mg/day
 Phosphate restriction compromises protein intake and
nutritional status
 Highly processed foods contain more easily absorbed
phosphate.
 Can keep phosphorus normal in CKD 3-5 & serve as
adjuvant to other methods in dialysis patients.
JASN March 2007 vol. 18 no. 3 875-885
Diet control

 Adequate dialysis or nocturnal dialysis
 Low calcium dialysis fluid (1.25 -1.5 mmol/l) to reduce
calcium-phosphate product.
 No evidence support clinically differences in phosphorus
removal among different dialysis membranes or dialyzers
in current routine use.
National kidney foundation K/DOQI linical practice guidelines, Evaluation and Treatment of
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) 2010.
Dialysis

Although many of the factors determining calcium and
phosphate control in haemodialysis patients are
unmodifiable, dialysate calcium concentration, the
duration of the dialysis session & haemodiafiltration all
had an impact on calcium, phosphate and PTH.
Davenport A, Gardner C, Delaney M. Do Differences in Dialysis Prescription Impact on KDOQI Bone
Mineral Targets? The Pan Thames Renal Audit Blood Purif. 2010 Aug 12;30(2):111-117
Dialysis prescription impact on
K/DOQI bone mineral target

 Aluminium-based – risk of toxicity
 Calcium-based – risk of metastatic calcification (due to
inability to excrete calcium, and low turnover bone
disease in some cases)
 Non-Ca2+/ Al based, effective but costly and large
numbers of tablets required, for examples Sevelemer
hydrochloride (Renegel); Lanthanum (Fosrenol).
JASN March 2007 vol. 18 no. 3 875-885
Phosphate binders

Phosphate Binding Agents In Routine
Clinical Practice & Their Ranked Cost

 Control hyperphosphatemia
 Lower LDL-cholesterol (1.68 vs 2.66 mmol/l)
 Lower percentage increase in coronary artery (5% vs.
25%), and aorta calcification (5% vs. 28%)
 Decrease in CRP
 Decrease uric acid
 Decrease fibroblast growth factor 23(FGF23)
Paolo Raggi, Slobodan Vukicevic, Rosa Maria Moysés, Katherine Wesseling, David M. Spiegel:Ten-
Year Experience with Sevelamer and Calcium Salts as Phosphate Binders, CJASN January 2010 vol.
5 no. Supplement 1 S31-S40
Sevelemer

The Renagel in New Dialysis (RIND) was a prospective, randomized study that compared
the effect of sevelamer and calcium-based binders After 4 yr, the mortality rate was
higher in calcium-treated patients (10.6 per 100 patient-years; 95% confidence interval
[CI] 6.3 to 14.9) than sevelamer-treated patients (5.3 per 100 patient-years; 95% CI 2.2 to
8.5; P = 0.05).
Raggi P et al. CJASN 2010;5:S31-S40

 Ergocalciferol (vit. D2), Cholecalciferol (vit D3)
 One-alpha calcidol (vitamin D prohormones 1-α-
hydroxyvitamin D3 and 1-α-hydroxyvitamin D2).
requires 25 hydroxylation in liver.
 Calcitriol (1,25 dihydroxy-D3)
 Vitamin D analogues (Paricalcitol, Doxercalciferol, 22-
oxacalcitriol)
 To suppress PTH secretion in low calcium states.
JASN March 2007 vol. 18 no. 3 875-885
Vitamin D Therapy

Recmended Suplementation Of Vitamin D
Deficiency / Insufficiency In Patients With CRF
Stage 3 & 4

 4.2.4. In patients with CKD stage 5D and elevated or
rising PTH, we suggest calcitriol, or vitamin D analogs, or
calcimimetics, or a combination of calcimimetics and
calcitriol or vitamin D analogs be used to lower PTH
(2B).
KDIGO Clinical Practice Guideline 2012 Diagnosis,
Evaluation, Prevention, and Treatment of Chronic Kidney
Disease –Mineral and Bone Disorder (CKD-MBD)

A “stepped-care” approach to the prevention and
treatment of 2 ndry hyperparathyroidism in CKD

 Risk of metastatic calcification
 Calcimimetics (calcium receptor agonists)
 Subtotal/total parathyroidectomy PTH > 88 pmol/l (>
800pg/ml) with raised Ca2+ and/or PO4 & refractory to
medical treatment.
Management of tertiary
hyperparathyroidism

• Increases the sensitivity of the calcium sensing receptor
in the parathyroid glands
• Dose 30 – 180 mg/day
• Reduced PTH, Ca2+, and PO4-
• Less likely to have parathyroidectomy, fracture &
cardiovascular hospitalizations.
• However, no studies have demonstrated that cinacalcet
offers a therapeutic benefit on mortality or vascular
events (KDIGO, 2009).
Cunningham J et al. Kidney Int 2005; 68: 1794K KDIGO Clinical Practice Guideline 2009
Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease –Mineral and Bone
Disorder (CKD-MBD).
Calcimimetics

Comparative Properties Of
Calcimimetic & Calcitriol Or Its Analogs

They found combination of cinacalcet and lower doses of
active vitamin D analogue significantly improved the
proportion of subjects achieving phosphorus control and
all three mineral management targets compared with the
practice of using primarily active D analogues alone.
David M. Spiegel, Lesley McPhatter, Ann AllisonA Computerized Treatment Algorithm Trial to
Optimize Mineral Metabolism in ESRD CJASN CJN.08170811 february 2012 doi:10.2215
Conclusion

 Normal: less than 20 mcg/l
 Aluminium toxicity: increase in aluminium level of > 50
mcg/l
 Desferioxamine infusions – note side effects
 High flux dialysis if level > 200 mcg/l
 Desferioxamine test: 5mg/kg in 100 ml saline over last
hour of dialysis; measure aluminium levels pre-dialysis,
and 40 hours later
Aluminum Toxicity

Osteoporosis & Bisphosphonates

Osteoporosis & Calcitonin

Alorgism for management of bone
disorder in CRF patients
Ca x ph
<55 >55
PTH N or
low N
PTH> 1-3N PTH >
target
=Stop
active vit D
=Low Ca
dialysate
= I Ca cont.
Ph binder
Cont.
Current ph
binder &
active vit. D
Increase
active vit.
D
PTH N or
low N
PTH N to
elevated
PTHgrossly
elevated
Consider
ADBD
=Stop
active vit D
=Low Ca
dialysate
= Ca free
Ph binder
Ca &Ph Subtotal
parathyroide
-ctomy
High ph High Ca
=Stop
active vit D
=Low Ca
dialysate
= Ca free
Ph binder
=Stop
active vit D
= dietary
ph
regimen
= increase
Ph binder
ADBD = Adynamic bone disease

Recommended Initial Dosing Of Vitamin D
Sterols By S. Level Of Ca, Ph, PTH&Ca P Prod.

Recommended Initial Dosing Of Vitamin D Sterols
By S. Level Of Ca, Ph, Pth&ca P Product Stage3 &4

Frequency For Monitoring
Serum Level Of Total Co2

Frequency Measurement Of S. Level Of
Ca, Ph, PTH After Renal Transplantation

 The prevalence of incident fractures among ESRD
patients is 10%-40%, with approximately 50% of
patients over the age of 50 having had a fracture
(Nephrology 2009;14:395-403).
 Studies suggest that dialysis patients are four times more
likely to suffer a fracture than the general populations
Summary

 Patients with CKD-5D have distinct risks for fracture, as
well as sharing risks identified in the general population.
 Bone mineral density measurement by dual-energy X-
ray absorptiometry is generally not helpful in HD
Patients..
Summary

The best prevention strategies include:
 Reviewing all medications
 Minimizing the use of psychotropic drugs whenever possible.
 Referring patients to physical therapists for gait/balance/strength
training.
 Referring patients to occupational therapists for safety
 recommendations
 Toussaint ND, Elder GJ, Kerr PG : A rational guide to reducing fracture risk in dialysis
patients. Semin Dial. 2010 Jan-Feb;23(1):43-54
Summary

Fractue in hd prof ahmed hassan

Fractue in hd prof ahmed hassan

Recommended

Recommended

More Related Content

What's hot

What's hot (19)

Similar to Fractue in hd prof ahmed hassan

Similar to Fractue in hd prof ahmed hassan (20)

Recently uploaded

Recently uploaded (20)

Fractue in hd prof ahmed hassan