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Dr Mampedi Bogoshi

Dr Mampedi Bogoshi. Osteoporosis. † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA. Discussion Points. Osteoporosis Burden of Disease Risk Factors Vitamin D and Calcium Recommendations and management. Peak bone mass between 25 and 35. Bones thicken

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Dr Mampedi Bogoshi

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  1. Dr Mampedi Bogoshi Osteoporosis †Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA

  2. Discussion Points • Osteoporosis Burden of Disease • Risk Factors • Vitamin D and Calcium • Recommendations and management

  3. Peak bone mass between 25 and 35. Bones thicken Bones are at their strongest From 35 to menopause bone mass slowly declines. Gradually your body starts to lose more bone than it makes. Bone development

  4. Osteoporosis Burden of Disease

  5. What is Osteoporosis? “….a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture”

  6. Risk factors for osteoporosis: • Age • Low Oestrogen • Women are at a greater risk than men, • Thin or have a small frame • White or Asian race • Women who are postmenopausal, including those who have had early or surgically induced menopause • Cigarette smoking, • Eating disorders such as anorexia nervosa or bulimia, low amounts of calcium in the diet, • Heavy alcohol consumption, • Inactive lifestyle, • Certain medications, e.g. corticosteroids and anticonvulsants • Rheumatoid arthritis itself is a risk factor for osteoporosis. • Family History

  7. Fracture Risk and Bone Quality • Bone quality may be defined as the ability of bone to resist fracture • Changes in the rate of bone turnover can affect mineralization, microarchitecture, and bone mass • Changes in key properties of bone can lead to alterations in bone strength and the ability of bone to resist fractures • The primary goal in treating osteoporosis should be fracture prevention Adapted from Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement. 2000;17(1):1–45; Miller PD et al J Clin Densitom 1992;2(3):323–342; Boivin GY et al Bone 2000;27(5):687–694; Dempster DW Osteoporos Int 2002;13(5):349–352.

  8. Bone Quality 4 bone properties affect bone strength: • BMD 2) Bone Turnover 3) Bone Microarchitecture 4) Bone Mineralisation

  9. How Key Properties of Bone Affect Fracture Risk BMD BoneStrength FractureRisk BoneTurnover Altersmicroarchitecture andbone mineralization Adapted from Garnero P et al J Bone Miner Res 1996;11(3):337–349; Miller PD et al J Clin Densitom 1999;2(3):323–342; Boivin GY et al Bone 2000;27(5):687–694.

  10. 1) Bone Quality

  11. Bone Turnover • Bone turnover (remodeling) is a continuous process of bone resorption followed by bone formation • Measured noninvasively by assessing biochemical markers of bone remodeling e.g. ALP • Higher bone turnover has been shown to be linked to increased rates of bone loss and increased risk of fracture • Patients with higher* bone turnover were 4.1 times more likely to suffer a fracture • Greater decreases in bone turnover are associated with lower risk of fracture** CTx=C-telopeptide of type I collagen; NTx=N-telopeptide of type I collagen *In a clinical study to evaluate markers of bone turnover as predictors of hip fracture in elderly women followed for 22 months**In a meta-analysis of 18 clinical trials of antiresorptive therapy to examine the association between BMD and risk of nonvertebral fractures Adapted from Kanis JA. Pathogenesis of osteoporosis and fracture. In: Osteoporosis. Malden: Blackwell Science, Inc., 1996:22–55; Miller PD et al J Clin Densitom 1999;2(3):323–342; Garnero P et al J Bone Miner Res 1996;11(10):1531–1538; Hochberg MC et al J Clin Endocrinol Metab 2002;87(4):1586–1592.

  12. 2) BMD

  13. How Key Properties of Bone Affect Fracture Risk BMD BoneStrength BoneTurnover FractureRisk Altersmicroarchitecture andbone mineralization

  14. Bone Mineral Density • BMD measurement is a noninvasive techniqueused to establish or confirm a diagnosis of osteoporosis and provide an assessment of fracture risk • 1 SD decrease in BMD has been shown to correlate with 1.5- to 2-fold increases in fracture risk • >80% of bone strength was related to BMDin two separate in vitro studies* *Two separate cadaveric studies of correlation between BMD and strength of the proximal femur and BMD and thoracic vertebral strength in elderly patients Adapted from National Osteoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 2003; Cummings SR et al Lancet 1993;341(8837):72–75; Bouxsein ML et al Bone 1999;25(1):49–54; Moro M et al Calcif Tissue Int 1995;56(3):206–209.

  15. Prospective Cohort Study Decreased BMD In Vivo Has Been Associated with Fracture Incidence • In a meta-analysis, the link between low BMD and fracture risk was similar to or stronger than • Diastolic blood pressure and stroke • Serum cholesterol and coronary disease 60 Spine Distal radius Calcaneus 50 40 Incidence of fractures(fractures per 1000 patient-years) 30 20 10 0 2 SD 1 SD Mean –1 SD –2 SD Bone mass Evaluation of relationship between bone mineral content of four skeletal sites to the incidence of vertebral fracture over six years in 699 postmenopausal women Meta-analysis of prospective cohort studies from 1985 to 1994 containing data on baseline BMD and fracture follow-up to determine whether BMD would predict fracture Adapted from Miller PD et al Calcif Tissue Int 1996;58(4):207–214; Wasnich RD et al J Nucl Med 1989;30(7):1166–1171; Marshall D et al BMJ 1996;312(7041):1254–1259.

  16. Two Separate Laboratory Studies Increases in BMD Lead to Greater Bone Strength In Vitro 8000 6000 r2=0.92 p<0.0001 r2=0.88 p<0.001 5000 6000 4000 Femoral failure load (N) T11 failure load (N) 4000 3000 2000 2000 1000 0 0 0 0.2 0.4 0.6 0.8 1.0 0 0.25 0.50 0.75 1.00 1.25 1.50 Trochanteric BMD (g/cm2) Lumbar spine (lateral) BMD (g/cm2) Test set-up to determine bone strength Schematic of material testing system to break vertebra Laboratory studies to determine correlation between BMD and bone strength in human cadaveric specimens Adapted from Bouxsein ML et al Bone 1999;25(1):49–54; Moro M et al Calcif Tissue Int 1995;56(3):206–209.

  17. 3) Microarchitecture

  18. How Key Properties of Bone Affect Fracture Risk BMD BoneStrength BoneTurnover FractureRisk Altersmicroarchitectureandbone mineralization

  19. Trabecular Bone Bone volume Trabecular thickness Trabecular number Horizontal struts Connectivity Plate perforation Cortical Bone Cortical porosity Cortical thickness Microarchitectural Changes in Osteoporosis Over Time

  20. Trabecular Bone Microarchitecture • Bone microarchitecture is assessed invasively to determine the bone’s structural parameters • Excessive bone resorption alters trabecular architecture and increases cortical porosity • By normalizing turnover, it may be possible to preserve bone microstructure and decrease cortical porosity Adapted from Thomsen JS et al Bone 2002;30(1): 267–274; Dempster DW Osteoporos Int 2002;13(5):349–352; Bell KL et al Bone 2000;27(2):297–304; Riggs BL, Melton LJ III J Bone Miner Res 2002;17(1):11–14; Boivin GY et al Bone 2000;27(5):687–694; Masarachia P et al. Posters presented at the 2003 American Society for Bone and Mineral Research meeting, Minneapolis, Minnesota, September 19–23, 2003; Roschger P et al Bone 2001;29(2):185–191.

  21. Assessing Trabecular Bone Microarchitecture • Iliac crest bone biopsy is an invasive procedure used to obtain bone samples from humans • Bone biopsy samples are used for evaluating trabecular microarchitecture by 2-D and (3D) micro-CT imagery • Trabecular microarchitecture changes have not been established to be predictive of fracture risk Adapted from Thomsen JS et al Bone 2002;30(1):267–274.

  22. Overall Limitations of Iliac Crest Biopsy • Iliac crest is not an osteoporotic fracture site • Histomorphometric parameters vary even at contiguous sites in the iliac crest • Intersample variation of bone volume from two contiguous sites was 15.7% in one study (n=55 patients)* • Histomorphometric parameters at the iliac crest correlate poorly with those at the spine and hip *Evaluation of intersample variation for an individual and for patient groups in two contiguous transiliac crest samples in 55 patients (mean age 55 years); Adapted from Chavassieux PM et al Calcif Tissue Int 1985;37(4):345–350; Thomsen JS et al Bone 2002;30(1):267–274.

  23. Consequences of Osteoporosis • Clinically, osteoporosis manifests in occurrence of characteristic low-trauma fractures, the best documented of these being hip, vertebral, and distal forearm fractures. Source: The burden of musculoskeletal conditions at the start of the new millennium: a report of a WHO scientific group. WHO Technical Report Series 919, World Health Organization, Geneva 2003.

  24. Epidemiology of Osteoporosis • Osteoporosis is known to increase with age. • Osteoporosis is more prevalent in women than men. Prevalence of osteoporosis for white female nursing home residents: Age Source: Zimmerman SI et al. The prevalence of osteoporosis in nursing home residents. Osteoporosis Int 1999;9:151-77.

  25. Increasing Risk of Osteoporotic Fracture in Women, by Age Source: Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. World Health Organ Tech Rep Ser 2003;919:i-x, 1-218, back cover.

  26. Hip Fracture Mortality Annual Mortality Rate Source: US Congress of Health Technology Assessment 1994, OTA-BP-H-120. US Government Printing Office, Washington DC.

  27. Vitamin D: Its Importance in the Treatment of Osteoporosis

  28. The Importance of Vitamin D • Vitamin D is essential for ensuring intestinal absorption of calcium • Lack of vitamin D leads to increased release of PTH and bone resorption • Evidence suggests that vitamin D inadequacy increases risk of fracture • Vitamin D inadequacy also increases the risk of falls PTH=parathyroid hormone Adapted from Parfitt AM et al. Am J Clin Nutr. 1982;36:1014–1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273–278; Lips P et al. J Clin Endocrinol Metab. 2001;86:1212–1221; LeBoff MS et al. JAMA. 1999;281:1505–1511; Bischoff HA et al. J Bone Miner Res. 2003;18:343–351; Gallacher et al. Curr Med Res Opin. 2005;21:1355–1361.

  29. Liver Intestine Bone Vitamin D Production UVB Sun ProD3  PreD3  Vitamin D3 Skin DietVitamin D3 Vitamin D2 25(OH)D Kidney Increase calcium and phosphorus absorption PTH (+) (+) Low PO2– Mobilize calcium stores 4 1,25(OH)2D Maintain serum calcium and phosphorus Metabolic functions Bone health Neuromuscular functions 25(OH)D=25-hydroxyvitamin D; PTH=parathyroid hormone; 1,25(OH)2D=1,25-dihydroxyvitamin D Adapted from Holick MF. Osteoporos Int. 1998;8(suppl 2):S24–S29.

  30. Sources of Vitamin D • Sunlight exposure • Major source of vitamin D, providing the majority of the body’s daily requirement • Vitamin D production is affected by season, duration of exposure, sunscreen use, and skin pigmentation • Endogenous production • Ability of skin, liver, and kidneys to form and process vitamin D • Dietary intake • Minor source of vitamin D • Vitamin D is rare in foods other than fatty fish, eggs, and supplemented dairy products* • Even vitamin D–fortified dairy products may not contain level indicated on label • Vitamin D can be supplied by multivitamins and supplements • Supplements containing vitamin D alone are not readily available • Patient compliance with supplementation therapy is inconsistent *Sold in the United States, Canada, Argentina (optional), Brazil, Guatemala, Honduras, Mexico, Philippines (optional), and Venezuela Adapted from Holick MF; Allain TJ, Dhesi J; Webb AR et al; Parfitt et al; Matsuoka LY et al; Holick MF; Lips P; Macleod CC et al; Omdahl JL et al; Chen TC et al; Holick MF et al; Heaney RP; Segal E et al; Webb AR et al; Faulkner H et al; Roche Vitamins Europe Ltd.

  31. Recommendations for Vitamin D Intake Europe The Scientific Committee for Food of the Commission of the European Communities recommends • 400 IU of vitamin D daily for the elderly (age 65) United States The Institute of Medicine has defined adequate daily intake of vitamin D according to age • Adults up to age 50 200 IU • Adults 51–70 400 IU • Adults >70 600 IU No toxic effects were reported in 48 of 50 adults with vitamin D deficiency given a single intramuscular dose of 600,000 IU annually in a clinical study to assess the efficacy and tolerability profile of high vitamin D intake. Adapted from European Commission. Report on Osteoporosis in the European Community:Action on Prevention. Luxembourg: Office for Official Publications of the European Communities, 1998; Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: Institute of Medicine, National Academy Press, 1997; Diamond TH et al. Med J Aust. 2005;183:10–12.

  32. Vitamin D Inadequacy* Has Important Consequences Calcium absorption Parathyroidhormone Bone mineraldensity Appropriateneuromuscularfunction Risk of fracture Artist rendition *Vitamin D inadequacy is defined as serum 25(OH)D <30 ng/mL. Adapted from Parfitt AM et al. Am J Clin Nutr. 1982;36:1014–1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273–278; Holick MF. Osteoporos Int. 1998;8(suppl 2):S24–S29; DeLuca HF. Metabolism. 1990;39(suppl 1):3–9; Lips P. In: Advances in Nutritional Research. New York, Plenum Press, 1994:151–165; Pfeifer M et al. Trends Endocrinol Metab. 1999;10:417–420; Heaney RP. Osteoporos Int. 2000;11:553–555.

  33. Vitamin D Is Essential for Calcium Absorption Results of 2 randomized, crossover studies conducted approximately 1 year apart in 34 postmenopausal women Calcium absorptiona 5 +65% 4 3 AUC (mghr/L) 2 1 0 Pretreated with vitamin Db (n=24) Not pretreated with vitamin Dc (n=22) aP<0.001bSerum vitamin D 32 ng/mLcSerum vitamin D 20 ng/mL Adapted from Heaney RP et al. J Am Coll Nutr. 2003;22:142–146.

  34. In a clinical study, Vitamin D Supplementation Decreased Fracture Risk • 5-year randomized, double-blind, controlled trial • N=2686 • Age 65 to 85 years • Vitamin D = 100,000 IU once every 4 months (equivalent to 800 IU/day) 1.2 P=0.02 1.0 –33% 0.8 Fracture relative risk(hip, wrist, forearm, spine) 0.6 0.4 0.2 0.0 Untreated (n=1341) Treated (n=1345) Adapted from Trivedi D et al. BMJ. 2003;326:469.

  35. Effect of Vitamin D and Calcium Supplementation on Risk of Falling • 122 women • Age: 63 to 99 years • Randomized, double-blind, controlled trial • Calcium 1200 mg/day • Calcium 1200 mg/day + vitamin D 800 IU/day • 12-week duration • Mean serum 25(OH)D 12 ng/mL at baseline Reduction in falls 1.2 P=0.01 1.0 0.8 –49% 0.6 Fall risk 0.4 0.2 0.0 Calcium only (n=44) Calcium + vitamin D (n=45) Adapted from Bischoff HA et al. J Bone Miner Res. 2003;18:343–351.

  36. According to a recent study, A High Prevalence of Vitamin D Inadequacy* Was Seen Across All Geographic Regions In a cross-sectional, international study in postmenopausal women with osteoporosis 81.8% 90 N=2589 80 71.4% 63.9% 70 60.3% 57.7% 53.4% 60 50 Prevalence (%) 40 30 20 10 0 All LatinAmerica Australia Asia Middle East Europe Regions *Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/mL. Study Design: Cross-sectional, international study of 2589 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution Adapted from Lips P et al. J Intern Med. In press.

  37. Reasons for High Prevalence of Vitamin D Inadequacy in Postmenopausal Women • Lack of sunlight exposure, including women who use sunscreen • Vitamin D is not common in the diet • Ability to synthesize vitamin D in the skin decreases with age • Lack of compliance taking daily supplements Adapted from Marcus R. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill Medical Publishing Division, 2001:1715–1743; Bringhurst FR. In: Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill Medical Publishing, 2005:2238–2249; Matsuoka LY. J Clin Endocrinol Metab. 1987;64:1165–1168; Parfitt AM. Am J Clin Nutr. 1982;36:1014–1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273–278; Holick MF et al. Lancet. 1989;2:1104–1105; MacLaughlin J, Holick MF. J Clin Invest. 1985;76:1536–1538; Resch H et al. Poster presented at: ECCEO; March 15–18, 2006; Vienna, Austria; Gaugris S et al. Poster presented at: ECTS and IBMS; June 25–29, 2005; Geneva, Switzerland; Hanley DA et al. Poster presented at: ECCEO; March 15–18, 2006; Vienna, Austria.

  38. Low Patient Compliance With Vitamin D Supplements • Fewer than 1 in 5 women with osteoporosis take vitamin D supplementationa • 33% of patients are taking supplements containing vitamin D onlyb • In Austria, where calcium and vitamin D supplementation are free to patients • 73% of patients take calcium and vitamin D combination supplements • 20% of patients take supplementation regularly aIn France, the United Kingdom, and Germany bIn the United Kingdom and Mexico Adapted from Gaugris S et al. Poster presented at: ECTS and IBMS; June 25–29, 2005; Geneva, Switzerland; Resch H et al. Poster presented at: ECCEO; March 15–18, 2006; Vienna, Austria.

  39. Summary of the Importance of Vitamin D in the Treatment of Osteoporosis • Vitamin D is essential for calcium absorption • Postmenopausal women have difficulty getting enough Vitamin D • Vitamin D inadequacy is widespread in postmenopausal women • Vitamin D supplementation has been shown to reduce the risk of fracture and falls Adapted from Parfitt AM et al. Am J Clin Nutr. 1982;36:1014–1031; Gaugris S et al. QJM. 2005;98:667–676; Bettica P et al. Osteoporos Int. 1999;9:226–229; Lips P et al. J Clin Endocrinol Metab. 2001;86:1212–1221; Lips P et al. J Intern Med. In press; Trivedi DP et al. BMJ. 2003;326:469; Bischoff HA et al. J Bone Miner Res. 2003;18:343–351.

  40. Bone turnover • The properties of bone quality are unfavorably altered by increased bone turnover. The consequences of increased bone turnover associated with osteoporosis can include: • Decreased bone mass • Decreased mineralization • Increased porosity • Disrupted architecture/trabecular connectivity • Biochemical markers are valuable tools in research investigations because they measure bone turnover. They are not commonly used in clinical practice for the treatment and management of osteoporosis.

  41. Nutrition facts • Packaged foods have a labels • Calcium supplements • Vitamin D = 400IU of vitamin D daily (milk, multivitamins and sunshine)

  42. Keeping your bones strong • Protein rich or salty foods • medications • inactivity • smoking

  43. Stay active • Resistance exercises • Weight bearing • Vary activities

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