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OSTEOPOROSIS PATHOPHYSIOLOGY, DIAGNOSIS AND MANAGEMENT

OSTEOPOROSIS PATHOPHYSIOLOGY, DIAGNOSIS AND MANAGEMENT . DR JAVAID MEHMOOD MALIK FRCP (UK), FACP (USA), FACR (USA) RHEUMATOLOGIST & MEDICAL SPECIALIST RAHMAT NOOR CLINIC RAWALPINDI. Quantitative -- bone mineral density. Normal < 1 SD Low bone mass / osteopenia

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OSTEOPOROSIS PATHOPHYSIOLOGY, DIAGNOSIS AND MANAGEMENT

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  1. OSTEOPOROSISPATHOPHYSIOLOGY, DIAGNOSIS AND MANAGEMENT DR JAVAID MEHMOOD MALIK FRCP (UK), FACP (USA), FACR (USA) RHEUMATOLOGIST & MEDICAL SPECIALIST RAHMAT NOOR CLINIC RAWALPINDI

  2. Quantitative -- bone mineral density • Normal < 1 SD • Low bone mass / osteopenia > 1 SD & < 2.5 SD • Osteoporosis > 2.5 SD • Severe or established osteoporosis fractures & > 2.5 SD

  3. Evolution of Osteoporosis The new definition of Osteoporosis given by NIH in 2001, shows that our understanding of this disease has evolved over time. According to new definition, Bone strength comprises of two elements i.e;Bone Quality + Bone Quantity Osteoporosis Leaders Meeting, January 16, 2005. Karachi

  4. Shifting the Osteoporosis ParadigmBone StrengthNIH Consensus Statement 2000 Bone Quality Bone Mineral Density Bone Strength and Architecture Turnover rate Damage Accumulation Degree of Mineralization Properties of the collagen/mineral matrix Adapted from NIH Consensus Development Panel on Osteoporosis. JAMA 285:785-95; 2001

  5. Current Definition of Osteoporosis Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality. Normal bone Osteoporosis NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95

  6. Resorption Cavities Osteoblasts Lining Cells Mineralized Bone Osteoid Bone Remodeling Process Osteoclasts Lining Cells Bone

  7. High Bone Turnover Leads to Development of Stress Risers and Perforations Osteoclasts Lining Cells Bone Stress Risers Perforations

  8. Risk Factors for Osteoporosis • Low trauma fracture since age 40 • Maternal history of osteoporotic fracture • Age > 65 • Thin body build (body weight < 57 kg) • Prolonged amenorrhea • Early menopause • Chronic corticosteroid use (> 6 months) • Disease predisposing to osteoporosis Meunier PJ , Clinical Therapeutics, 1999

  9. Osteoporosis: The Size of the Problem • Highly prevalent - affects 75 million people worldwide1 • 1/3 of women aged 60 to 70 • 2/3 of women aged 80 or older • Approximately 20-25% of women over the age of 50 have one or more vertebral fractures2 United States: 25%3 Australia: 20%4 Western Europe: 19%5 Denmark: 21%6 Scandanavia: 26%5 4. Jones G et al., Osteoporos Int 1996;6:233-9 5. O'Neill et al., J Bone Miner Res 1996;11:1010-8 6. Jensen GF et al., Clin Orthop 1982;166:75-81 1. Am J Med 1991;90:107-10 2. Melton LJ 3rd et al. Spine 1997;22:2S-11S 3. Ettinger B et al., J Bone Miner Res 1992;7:449-56

  10. 40 30 20 10 Vertebrae Annual incidence per 1000 women Hip Wrist 50 60 70 80 Age (Years) Incidence Rates for Vertebral, Wrist and Hip Fractures in Women After Age 50 Wasnich RD: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th edition, 1999

  11. Antiresorptive Agents Increase Bone Mass by Decreasing Remodeling Space and/or Prolonging Mineralization Antiresorptive Agent Remodeling space Newly formed bone Increased Mineralization

  12. Physiological Range Bone Strength Bone Turnover What Is the Optimal Reduction in Bone Turnover for an Antiresorptive Drug? • Insufficient turnover • Accumulation of microdamage • Increased brittleness due to excessive mineralization • Excessive turnover • Increase in stress risers (weak zones) • Increase in perforations • Loss of connectivity Adapted from Weinstein RS, J Bone Miner Res 2000; 15 621.

  13. Bone Turnover, Mineralization, and Bone Quality • There is a complex relationship between bone turnover and bone quality • Decrease of bone turnover • Increases mineralization • Permits filling of remodeling space Excessive suppressionIncreased mineralization Accumulation of microcracks Increased brittleness Skeletal fragility

  14. The Optimal Effect of an Antiresorptive Agent on Bone Quality Adequate suppression of bone turnover Physiologicalrepair of microdamage Sufficient mineralization Preservation of architecture Long-term efficacy and safety

  15. “The Domino Effect”

  16. Bone Turnover Markers • Bone turnover markers are components of bone matrix or enzymes that are released from cells or matrix during the process of bone remodeling (resorption and formation). • Bone turnover markers reflect but do not regulate bone remodeling dynamics.

  17. Urinary Markers of Bone Resorption Marker Abbreviation Hydroxyproline HYP Pyridinoline PYD Deoxypyridinoline DPD N-terminal cross-linking telopeptide of type I collagen NTX C-terminal cross-linking telopeptide of type I collagen CTX Delmas PD. J Bone Miner Res 16:2370; 2001

  18. Serum Markers of Bone Turnover Abbreviation Formation Bone alkaline phosphatase ALP (BSAP) Osteocalcin OC Procollagen type I C-propeptide PICP Procollagen type I N-propeptide PINP Resorption N-terminal cross-linking telopeptide of type I collagen NTX C-terminal cross-linking telopeptide of type I collagen CTX Tartrate-resistant acid phosphatase TRAP Delmas PD. J Bone Miner Res 16:2370, 2001

  19. Effects of the Rate of Bone Turnover on Bone Quality • State of mineralization • Accumulation of microdamage or fatigue damage

  20. Drug Treatment of Osteoporosis & Fracture Prevention • SERMs • Bisphosphonate • Calcitonin • HRT • Calcium & Vit D • Teriperatide • Strontium ranelate

  21. Presentation of Osteoporosis in a Post Menopausal woman • Fractures • Radiological osteopenia • Low bone mineral density • Acute back pain • Chronic backache • Bone pains

  22. Case 1 • 55 years old postmenopausal woman presents for routine check up • 5’4” and 57 kg • Mother had osteoporotic fracture of hip • Exercises regularly • BMD: Total T score hip –0.83, T score femoral neck –1.55, T score spine –1.01

  23. BMD = Mild osteopenia Risk factors – postmenopausal, low body weight, family hx of osteoporotic fx, ERT if having menopausal sx Increase calcium intake Continue exercise Repeat BMD scan in 2 yrs Discussion

  24. Case 2 • 29 year ol about to start chronic glucocorticoid therapy, Prednisolone 10 mg od, for severe asthma • No other medical problems, non-smoker, no family hx of fractures • BMD: T score hip –1.08, T score spine - 2.97, Z score spine –2.47

  25. Discussion • BMD = Osteoporosis • Z score <-2 (think about secondary cause) • Additional evaluation: low 24-hour urine calcium and borderline low 25-OH vitamin D • Consider occult malabsorption in pt’s with low bone density and low urinary calcium

  26. Discussion (case 2 cont’d) • Pt’s starting on long term steroids (> 1 month, 7.5 mg qd) should be considered for a bisphosphonate • Bone loss is rapid with steroid use • Measure BMD prior to starting tx for baseline • Minimize steroid use: decrease dose, use inhaled steroids (inhaled steroids do have effect on bone density)

  27. Case 3 • 62 year old woman is referred for backache • History of kidney stones • Family history of osteoporotic fracture • BMD: T score hip –2.03, T score spine –2.58

  28. BMD = Osteoporosis H/O kidney stones Measure serum Ca to screen for hyperparathyroidism Order 24 hr urine ca or urine ca/creat ratio If 24h is >200mg/d or spot ca/cr is >0.16 then HCTZ can be added to decrease urinary calcium excretion. Discussion

  29. Case 4 • 57 yo male presents with back pain. X-ray shows thoracic compression fracture • No other medical problems, taking no meds • 50 pack yr smoker • Testosterone 200ng/dl (nl 300-1000) • BMD: T score hip –2.49, T score spine –3.11

  30. Check LH and FSH Primary hypogonadism: high LH and FSH Secondary hypogonadism: low LH and FSH Further work-up should include an MRI of the pituitary to r/o tumor Testosterone 300mg IM q3weeks or 200mg q2weeks Contraindicated in men with BPH or prostate cancer Side effects: acne, sleep apnea, increased hemoglobin, and hot flashes Discussion

  31. Case 5 • 52 year old male presents with recurrent left rib pain • Had rib fracture 2 months prior secondary to “coughing” • No medical problems, not taking any meds, non-smoker • BMD: T score hip –0.90; T score spine –5.01, Z score spine –4.02

  32. Discussion • Fracture in the setting of no risk factors raises the suspicion for secondary causes of osteoporosis as does a Z score <-2 • TSH, calcium, phosphorus, alkaline phophatase, testosterone were wnl • UPEP and SPEP revealed a monoclonal spike, bone marrow biopsy confirmed dx of multiple myeloma • Pt started on a bisphosphonate – helps with hypercalcemia and also helps to decrease bone pain

  33. Case 6 • 54 year old female with h/o breast cancer five years ago presents with back pain • Also c/o frequent hot flashes • PMH significant for pulmonary embolus • Currently taking no meds, prior smoker • Strong family h/o osteoporosis • BMD: T score spine –2.66, T score hip –2.17

  34. BMD = Osteoporosis With h/o breast ca must r/o metastases as cause of back pain Can not use ERT b/c of h/o breast cancer and PE Can not use SERMS b/c of h/o PE Treat with bisphosphonate Discussion

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