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 • Increasingly becoming a global problem-most common metabolic bone d’se afflicting approx. 200m worldwide.
This definition applies to postmenopausal women and men >50yrs • T-Score= patient’s BMD BMD of control subjects who are at their peak BMD • Z-Score=patient’s BMD BMD of patients matched for age and sex Z-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 childhood • Bone loss • Aging with loss of gonadal function • Bone 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 GIT • Bone resorption exceeds bone formation from 3rd decade • Women lose-30-40% of cortical bone -50% of trabecular bone • Men 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 gut • Compensatory 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 fractures • Mostly from low-energy trauma/minor loads • Vertebral 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) JUVENILE • Children/young adults; both sexes • 8-14 yrs • Normal gonadal function • Hallmark: abrupt bone pain/ fracture following minor trauma
(B) IDIOPATHIC • PMO(TYPE 1)-high-turnover osteoporosis • Women>50-65yrs • Phase of accelerated bone loss primarily trabecular bone • Predorminantly increased osteoclastic activity • Fracture vertebrae and distal forearm common • Vertebral # 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 bone • Wrist, vertebrae and hip fractures common
STAGES • STAGE 1: loss of horizontal trabeculations • STAGE 2: loss of vertical trabeculae • STAGE 3: loss of both horizontal and vertical trabeculae with resultant cavitation of the vertebral body
RISK FACTORS National Osteoporosis Foundation (NOF) classifies them into: • Modifiable: • physical inactivity • drugs, alcohol, cigarette smoking • deficiency states • Thin build/small stature(body wght <127lbs/ BMI<20-25 kg/m² in men), • >10% body weight loss in men • Androgen deprivation therapy in men • Previous fragility fracture
b) Non-modifiable: • age (>50yrs) • sex(F:M=4:1) • race(caucasian/asian) • genetics(+ve family history) • amenorrhoea, late menarche, early menopause • post-hysterectomy and oophorectomy, • androgen/ estrogen def.
Pneumonic=OSTEOPOROSIS • O=lOw ca2+ • S=Seizure drugs • T=Thin build • E=Ethanol intake • O=hypOgonadism • P=Previous fracture • 0=thyrOid excess • R=Race • O=Other realtives with osteoporosis • S=Steroids • I=Inactivity • S=Smoking
EPIDEMIOLOGY • 10m Americans affected(80% women)-NOF • 34M have ↓ bone mass with ↑ risk for osteoporosis • 1.5m-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
Osteoporosis-related fractures result in annual direct expenditure of $12.2b-17.9b • Leading cause of fractures in the elderly • Women>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 slowly • Associated with ↑morbidity and mortality • Mortality also correlates with number of vertebral # • Often occurs with minimal stress • Mostly 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 pain • Paravertebral muscle spasm exacerbated by activity/ reduced by lying supine.
Complications: • Chronic pain • ↑morbidity and mortality • ↓ QOL • Prolonged immobility • Severe kyphosis • Spinal deformities→”dowager’s hump”→loss of 1-2’ of height by 7th decade of life • Loss of self-esteem→depression
PHYSICAL EXAM • Inspection • Palpation • Height measurement • Active/passive ROM • Neurological 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 • Osteogenesisimperfecta • 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 age • For men, not carried out routinely US preventive Services Task Force(USPSTF)/ American College of Physicians(ACP) recommendations: Indications for screening in men • Those with 10yr risk for osteoporotic # equal to or greater than that for 65yr old women who have no additional risk factors
INVESTIGATIONS • LAB WORKUP • 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+ levels • PTH level • Testosterone/gonadotropin level • ESR/ CRP • Urinary free cortisol levels/ dexamethasone suppression test • BMA • Serum/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 osteoporosis • Carboxyterminal 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 phosphatase • N-Telopeptide of collagen cross-links(NTx) • C-telopeptide of collagen cross-links(CTx)
URINARY MARKERS OF BONE RESORPTION • Hydroxyproline • Free and total pyridinolines(Pyd) • Free and total deoxypyridinolines(Dpd) • NTx • CTx
iii) IMAGING • 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) Densitometry • 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