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METABOLIC DISEASE OF SPINE-OSTEOPOROSIS. Presenter: DR.LEMAYIAN PETER Supervisor: DR. OMBACHI. Skeletal d’se characterised by:. Low bone mass Micro-achitectural breakdown of bone tissue. “silent killer” Preventable d’se Devastating physical, psychosocial and economical consequence - PowerPoint PPT Presentation
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PRESENTER: DR.LEMAYIAN PETERSUPERVISOR: DR. OMBACHI
METABOLIC DISEASE OF SPINE-OSTEOPOROSIS
Skeletal d’se characterised by:
Low bone massMicro-achitectural breakdown of bone
tissue
“silent killer”Preventable d’se Devastating physical, psychosocial and
economical consequenceIncreasingly becoming a global problem-
most common metabolic bone d’se afflicting approx. 200m worldwide.
WHO DEFINITION:
DEFINITION BMD MEASUREMENT
T-SCORE
NORMAL Within 1SD of mean BMD for young adult women
T-score >-1
OSTEOPAENIA BMD 1-2.5 SD below the mean for young adult women
T-Score btn -1 and -2.5
OSTEOPOROSIS BMD >2.5 SD below mean for young adult women
T-Score <-2.5
SEVERE OSTEOPOROSIS
BMD >2.5 SD below mean for young adult women in a patient who has already experienced >1 fractures
T-Score <-2.5 with fragility fractures
This definition applies to postmenopausal women and men >50yrs
T-Score= patient’s BMD BMD of control subjects who are
at their peak BMDZ-Score=patient’s BMD BMD of patients matched for age
and sexZ-Scores used in premenopausal women,
children and men<50yrs
PATHOPHYSIOLOGY
HALLMARK: reduced skeletal mass due to imbalance btn bone resorption and formation
Failure to build bone reserve from childhoodBone lossAging with loss of gonadal functionBone loss accelerates rapidly in women
during the first years after menopause
a) Estrogen deficiency leads to…
↑ expression of RANKL by osteoblasts↓ release of OPG↑recruitment of pre-
osteoclasts→↑differentiation and prolonged survival of osteoclasts via IL-1,IL-6,TNFᾳ.
T-Cells inhibit osteoblastic differentiation and activity with premature apoptosis of osteoblasts through cytokines e.g. IL-7
Increased sensitization of bone to the effects of PTH
↑osteoclastic apoptotic activity via ↑production of TGFᵝ
b) Aging
Progressive ↓ in supply of osteoblasts Reduced Ca2+ uptake from GITBone resorption exceeds bone formation from
3rd decadeWomen lose-30-40% of cortical bone -50% of trabecular boneMen lose-15-20% of cortical bone -25-30% of trabecular bone
c) Ca²⁺deficiency
→2° hyperPTH -↓ renal excretion of Ca2+ -↑ renal production of 1,25-
(OH)2-D (calcitriol)→↑ca2+ absorption from the gut
→↑bone resorption
d) Vit D Deficiency
Impaired absorption of Ca2+ from gutCompensatory mechanism:-Leads to
hyperPTH→↑production of calcitriol from the kidneys
PTH and vit.D have their effect on bone being mediated via binding to osteoblasts and stimulating RANK/RANKL pathway
Osteoclasts do not have receptors for Vit.D or PTH
Osteoporotic Fractures
Aka Insufficiency/ fragility fracturesMostly from low-energy trauma/minor loadsVertebral bodies-1rly cancellous with
interconnected horizontal and vertical trabeculae.
In osteoporosis there’s ↓ in both bone mass and this internal interconnectivity(BUT preferentially disruption is in the horizontal trabeculae)→? Reason→?overaggresive osteoclastic resorption
Rosen and Tenenhouse cadaveric study:
As many as 200-450 horizontal trabeculae fractures per vertebral body in various stages of healing→cumulatively leads to weakening of cancellous bony structure
Osteoporosis Vs Osteomalacia
Normal human skeleton→60% mineral 40% organic material
(collagen)Osteoporosis-mineral: collagen ratio within
normal tho’ both are significantly ↓; bone is porous and brittle
Osteomalacia-mineral is reduced relative to organic content; bone is soft.
Classification of osteoporosis:
Localised 1°
Generalised 2°
1° Osteoporosis
(A) JUVENILEChildren/young adults; both sexes8-14 yrsNormal gonadal functionHallmark: abrupt bone pain/ fracture
following minor trauma
(B) IDIOPATHIC
a)PMO(TYPE 1)-high-turnover osteoporosisWomen>50-65yrsPhase of accelerated bone loss primarily
trabecular bonePredorminantly increased osteoclastic activityFracture vertebrae and distal forearm
commonVertebral # occur more often in the 7th decade
of life.
b) age-related/senile osteoporosis(TYPE 2)
-Low-turnover osteoporosis-gradual slow down in osteoblastic activity.Men and women >70 yrs Fractures in cortical and trabecular boneWrist, vertebrae and hip fractures common
2° Osteoporosis
CAUSE EXAMPLES
GENETIC/CONGENITAL Renal hypercalciuria, cystic fibrosis, ehler’s danlos, gauchers, marfans sx,osteogenesis imperfecta, hypoPO4²
ENDOCRINOPATHIES Cushing’s sx, DM,adrenal insuff., prolactinomas, hyperthyroidism, hyper-PTH, Hypogonadism, panhypopituitarism, klinefelter’s, turner’s sx
DEFICIENCY STATES Ca2+, Mg2+, Vit. D def, protein def., celiac d’se, malabsorption, malnutrition, parenteral nutrition
INFLAMMATORY CONDITIONS IBD, R.A., SLE, Ankylosing spondylitis
HAEMATOLOGICAL/ NEOPLASTIC DISORDERS
Haemophilia,, haemochromatosis, leukaemia, lymphoma, multiple myeloma, SCD, Thalassaemia, metastases
MEDICATIONS Anticonvulsants(Rx-induced Vit D def), antipsychotics, ARVS, Aromatase inhibitors(Anastrozole), anticancer drugs, Frusemide, Glucorcoticoids( PDN>5mg OD for >3/12), longterm Heparin, Li, SSRI, Hormonal therapies-Thyroxine, LHRH analogues
MISCELLANEOUS Pregnancy, lactation, alcoholism, depression, HIV/AIDS, CRD, CCF, Chronic liver disease, amyloidosis, prolonged immobility/disuse, Multiple sclerosis
STAGES
STAGE 1: loss of horizontal trabeculationsSTAGE 2: loss of vertical trabeculaeSTAGE 3: loss of both horizontal and vertical
trabeculae with resultant cavitation of the vertebral body
RISK FACTORS
National Osteoporosis Foundation (NOF) classifies them into:
a)Modifiable: physical inactivitydrugs, alcohol, cigarette smokingdeficiency statesThin build/small stature(body wght
<127lbs/ BMI<20-25 kg/m² in men), >10% body weight loss in menAndrogen deprivation therapy in menPrevious fragility fracture
b) Non-modifiable:
age (>50yrs)sex(F:M=4:1)race(caucasian/asian)genetics(+ve family history)amenorrhoea, late menarche, early
menopausepost-hysterectomy and oophorectomy,androgen/ estrogen def.
Pneumonic=OSTEOPOROSIS
O=lOw ca2+S=Seizure drugsT=Thin buildE=Ethanol intakeO=hypOgonadismP=Previous fracture0=thyrOid excessR=RaceO=Other realtives with osteoporosisS=SteroidsI=InactivityS=Smoking
EPIDEMIOLOGY
10m Americans affected(80% women)-NOF34M have ↓ bone mass with ↑ risk for
osteoporosis1.5m-2m osteoporotic fractures/yr (700,000
spinal #; 300,000 hip #; 200,000 wrist #)1 in every 2 women and 1 in every 5 men will
eventually experience osteoporotic #Men have a higher prevalence of 2°
osteoporosis
RACIAL DEMOGRAPHICS
RACE SEX(AGE>50YRS)
% ESTIMATED TO HAVE OSTEOPOROSIS
% ESTIMATED TO HAVE LOW BONE MASS
NON-HISPANIC WHITE;ASIAN
WOMEN 20 52
MEN 7 35
NON-HISPANIC BLACK
WOMEN 5
MEN 4 19
HISPANIC WOMEN 10 49
MEN 3 23
Osteoporosis-related fractures result in annual direct expenditure of $12.2b-17.9b
Leading cause of fractures in the elderlyWomen>50yrs have about 50% lifetime
fracture rate due to osteoporosis and about 80% of all fractures in pple aged >50yrs.
prognosis
Good if bone loss is detected early Incase of #→ may lead to chronic pain,
disability, prolonged immobilisation, death
Vertebral compression fractures
2/3 are asymptomatic and occur slowlyAssociated with ↑morbidity and mortalityMortality also correlates with number of
vertebral #Often occurs with minimal stressMostly affected-middle/lower thoracic and
upper lumbar
As posture worsens and kyphosis progresses→difficulty with balance, back pains, resp. compromise,↑ risk of pneumonia
↓ QOL
Presence of a # at one vertebral level→5-fold ↑ risk of getting another
CLINICAL PRESENTATIONS
Episode of acute back pain after bending, coughing,lifting, a fall, minor trauma
Pain-sharp, nugging, dull; exacerbated by movt; may radiate to the abdomen
Progressive kyphosis with loss of height+/- localised painParavertebral muscle spasm exacerbated by
activity/ reduced by lying supine.
Complications:
Chronic pain↑morbidity and mortality↓ QOLProlonged immobilitySevere kyphosisSpinal deformities→”dowager’s hump”→loss
of 1-2’ of height by 7th decade of lifeLoss of self-esteem→depression
PHYSICAL EXAM
InspectionPalpationHeight measurementActive/passive ROMNeurological exam
Signs esp in the elderly that may indicate ↑risk of a fall-gait problems, orthostatic hypotn, LL weakness, cognitive impairment
Findings of subtle collagen defects:-short 5th digit, dentinogenesis imperfecta, hyperlaxity, hearing loss, pes planus, bunions, blue sclera
DDX
Osteomalacia Tumors(osteolytic) Infections Osteonecrosis Other bone-softening metabolic disorders Mets Leukaemia/lymphoma Osteogenesis imperfecta Renal osteodystrophy Multiple myeloma Scurvy Paget’s disease Sickle cell anaemia Homocystinuria/homocystinaemia
WHO-Fracture-Risk algorithm(FRAX)
Developed to calculate 10yr probability of any major osteoporotic # in a given patient
Take into a/c BMD and other clinical risk fxtrs
NOF recommends RX for patients with WHO-10yr-probability of major osteoporosis-related # of >20% (or >30% for hip #)
This algorithm is useful in identifying patients most likely to benefit from Rx.
SCREENING
Women >50yrs of ageFor men, not carried out routinelyUS preventive Services Task Force(USPSTF)/
American College of Physicians(ACP) recommendations:
Indications for screening in menThose with 10yr risk for osteoporotic # equal
to or greater than that for 65yr old women who have no additional risk factors
INVESTIGATIONS
i) LAB WORKUPa) To establish baseline conditions:-CBC-Serum Ca²⁺,mg²⁺,po4-,Fe2+/ferritin levels-LFTs-TFTs-Vit. D levels-Cr/BUN
b) To exclude 2° causes
24 hr-urinary Ca2+ levelsPTH levelTestosterone/gonadotropin levelESR/ CRPUrinary free cortisol levels/ dexamethasone
suppression testBMASerum/Urinary protein electrophoresis
ii) Biochemical markers of bone turnover
Reflect bone formation and resorption
Maybe ↑in high-bone turnover states and may also be useful in some patients for monitoring early response to treatment
SERUM MARKERS OF BONE FORMATION
Bone specific alkaline phosphatase(BSAP)Osteocalcin(OC)-if high, indicates a high
turnover osteoporosisCarboxyterminal propeptide of type 1
collagen(PICP)Aminoterminal propeptide of type 1
collagen(PINP)
SERUM MARKERS OF BONE RESORPTION
Cross-linked C-Telopeptide of type 1 collagen(ICTP)
Tartrate-resisitant acid phosphataseN-Telopeptide of collagen cross-links(NTx)C-telopeptide of collagen cross-links(CTx)
URINARY MARKERS OF BONE RESORPTION
HydroxyprolineFree and total pyridinolines(Pyd)Free and total deoxypyridinolines(Dpd)NTxCTx
iii) IMAGING
(a) Plain radiography-to assess overall skeletal intergrity-suspected #-if patient has lost>1½” of height Can suggest presence of osteopaenia or
bone loss though cannot diagnose osteoporosis
Osteoporosis predorminantly affects trabecular bone rather than cortical bone
Cortical bone not affected by osteoporosis until >30% of bone loss has occurred
30-80% of bone mineral must be lost before radiographic lucency becomes apparent.
(b) Densitometry1)Dual-Energy X-Ray
Absorptiometry(DXA)-quantifies bone loss-standard for evaluation of BMD-not as sensitive as QCT for detecting early
trabecular bone loss, but it provides rapid scanning times, is less costly and precise
-used to calculate BMD at the lumbar spine, hip,prox. Femur and wrist
-data is reported as T and Z-scores
2) Single-photon Absorptiometry(SPA)
-precise and with low- radiation exposure
-relatively insensitive for detecting early-stage osteoporosis coz it measures cortical rather than trabecular bone.
3) Dual-Photon Absorptiometry(DPA)
-Can measure BMD in the spine and prox. Femur
-limited by poor reproducibility, prolonged scanning times and artifacts caused by vascular calcifications.
4) Computed Tomography
Quantitative CT Scanning(QCT)-assesses BMD only at the spine-can be used in both adults and children-is the most sensitive method for diagnosing
osteoporosis coz it measures trabecular bone within the vertebral body.
-cf with DXA, is more expensive, poor reproducibility, possible interference by osteophytes, higher radiation dose
Single-Photon Emission CT Scanning(SPECT)
-CT-Like bone imaging technique that offers better image contrast and more accurate lesion localisation
-increases sensitivity and specificity of bone scanning for detection of lumbar spine lesions by 20-50% over planar techniques
-visualise bony structures that would overlap on planar images e.g. facet joints, pars interarticularis, pedicles
5) U/S
Quantitative U/S of the Calcaneus(QUS)
-The heel is the only validated skeletal site for clinical use of QUS in osteoporosis mx.
-low cost, no radiation
-not as accurate.
6) MRI-Useful in discriminating btn acute and
chronic fractures of the vertebrae and occult fractures of the proximal femur.
7) Bone Scanning(99m Tc)
8) Bone biopsy and histology
MANAGEMENT
Approach considerationsRx is aimed at # prevention and rehabilitation.-lifestyle modification-pharmacotherapy-Rx of potentially-treatable 2° causes-surgical Mx of vertebral compression #-rehabilitation to control pain.
PHARMACOTHERAPY
NOF Recommendations:Pharmacotherapy should be reserved for
postmenopausal women and men >50yrs presenting with:
hip/vertebral #T-score of -2.5 or less at the femoral neck or
spinelow bone mass(T-score of btn -1.0 and -2.5 at
the femoral neck or spine)
10yr probability of a hip # of >3% or
10yr probability of a major osteoporosis-related # of >20% based on FRAX
ADVISABLE THAT ALL RX SHOULD BE GIVEN WITH CA2+ AND VITAMIN D SUPPLEMENTS
1. BIPHOSPHONATES
Most commonly usedFor Rx and prevention Oral and I.V. formulationsMOABinds to the hydroxyarpatite crystalls at active
bone resorption sites thereby inhibiting osteoclastic resorption.
S/E
Overtime, it ↓bone turnoverAt very high levels, ↓bone strength and
resilienceOsteonecrosis of the jawAtypical femur fractures(transverse subtroch
and shaft #)
Bone turnover markers should be monitored and if they become significantly ↓, the treatment holidays instituted until return to normal levels
i. Alendronate(Fosamax)
-dose : 70mg/wk PO
-↓ fracture rate of the spine, hip and wrist by 50%
-can be combined with Vit. D(Fosamax-Plus D)
ii) Risendronate(Actonel)-↓ vertebral fractures by 41% and non-
vertebral fractures by 39% over 3 yrs
-can be combined with Ca2+
iii) Ibandronate
-PO once monthly or IV 3-monthly
iv) Zolendronic Acid(Reclast)-most potent-↑ BMD at the spine by 4.3-5.1% and hip by
3.1-3.5%-↓ spine # by 70% and hip by 41%-given IV once yearly
2. SELECTIVE ESTROGEN RECEPTOR MODULATORS( SERM)
RALOXIFENE(Evista)-↓ risk of vertebral fractures by 35%
3. PTH
TERIPARATIDE(human recombinant PTH)MOA: ?stimulation of angiogenesis→vascular
endothelial stem cells differentiated to become osteoblasts
indications Rx of osteoporosis where other Rx has failed
or intolerance has developed
Finkelstein et al: combination therapy with biphosphonates has ↓benefits
Cosman et al: 3/12-on followed by 3/12-off pulses of teriparatide in pts on weekly Alendronate→BMD increased above that of either Rx alone.
4. CALCITONIN
MOA: ↓osteoclastic activity-reserved for those intolerant to estrogens
-Formulations: Inj or Intranasal spray (200i.u. OD)
5. DENOSUMAB
Humanised monoclonal Ab against RANKLDOSE: 60mg SQ every 6/12May become 1st line of Rx for patients with
autoimmune and inflammatory disorders coz overactivity of RANKL is a major factor in bone loss in such pts.
6. HRT
Currently not recommended coz of S/E(ca breast, MI, CVA, DVT)
i) Estrogen Derivatives-premarin, Estradiol, Estropipate
ii)Estrogen-Progestin combinations:-Estradiol-Levonorgesterol-conjugated Estrogen/medroxyprogesterone
acetate
7. OTHERS
Vitamin-D formulations:ergocalciferol(Vit D2), cholecalciferol(Vit D3)
Ca2+ salts: ca-citrate, ca-carbonate
Strontium ranelate
Daily nitroglycerin ointment
American association of clinical endocrinologists
1st line: alendronate, risendronate, zolendronic acid, denosumab
2nd line: ibandronate3rd line: raloxifeneTreatment failure: teriparatide
SURGICAL THERAPY
OBJECTIVE: early mobilisation and return to normal or near normal function
INDICATIONS: incapacitating/ persistent severe focal back pain related to vertebral collapse
i) Anterior and posterior decompression and stabilisation with pedicle screws, rods, plates, cages +/- bone grafting to achieve fusion
ii) KYPHOPLASTY Reduces amount of kyphosis and restores
vertebral body height Minimally invasive
iii) VERTEBROPLASTY
-Useful to control pain associated with vertebral #
-fuses fracture fragments into one block using acrylic cement, preventing painful mvt of individual fragments.
-also reduces pain by heat produced by polymerization process as the cement hardens
-does not restore height of compressed vertebral body
DIETARY MEASURES
Oral Vit. D and Ca2+ supplements daily intake for osteoporotic patients:
-Ca2+: 1200-1500mg-Vit. D: 400-800i.uSources of Ca2+ : dairy products, nuts,
sunflower seeds, vegsVit D sources: eggs, liver, fatty fish, milk
OTHER RX MODALITIES
PHYSIOTHERAPY-to strengthen back extensor muscles to
↓kyphosis-orthotics: -Thoracolumbosacral
orthotics(TLSO) -Jewett brace -Cruciform ant spinal
hyperext(CASH) brace
OCCUPATIONAL THERAPY-training in performance of activities of daily
living
EXERCISES-aerobic, low-impact exercise(3-5 sessions/wk
each 45-60min)
PREVENTION OF OSTEOPOROSIS
Starts in childhoodAdequate ca2+/vit D intake/ weight-bearing
exercises2-pronged:i) Behaviour modification-cigarette smoking -physical
inactivity -intake of
alcohol,caffeine, animal protein
ii) Pharmacological
-regular periodic bone densitometry(every 2 yrs for postmenopausal women)
-Longterm monitoring-DXA repeated every 2-3 yrs if baseline is normal and every 1-2yrs in osteoporotic patients undergoing Rx.
END!
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