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  1. 1. Dr. Muhammad Khairussyakirin b Mohd Ali
  2. 2.  A skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. ◦ Bone strength reflects the integration of bone density and bone quality  Bone density (g/cm2 or g/cm3)  determined by peak bone mass and amount of bone loss.  Bone quality  architecture, turnover, damage accumulation, and mineralisation of the bone
  3. 3.   The spine, hips, ribs, and wrists are common areas of bone fractures from osteoporosis. Classification is based on bone mineral density (BMD). ◦ Osteoporosis is defined by BMD of less than –2.5 SD from the young adult mean (T-score)
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  5. 5.     T score: standard deviation of the BMD from the average sex matched 35-year-old For every 1 decrease in T score, double risk of fracture 1 SD decrease in BMD = 14 year increase in age for predicting hip fracture risk Regardless of BMD, patients with prior osteoporotic fracture have up to 5 times risk of future fracture!
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  7. 7.  In our community, the Chinese had the highest incidence of hip fractures compared to the Malays and Indians. ◦ Chinese women accounted for 44.8% of hip fractures
  8. 8.   Bone is continually remodeled throughout our lives . Bone resorption is always followed by bone formation, a phenomenon referred to as coupling Bone strength is determined by collagenous proteins (tensile strength) and mineralized osteoid (compressive strength). The greater the concentration of calcium, the greater the compressive strength
  9. 9.   Osteoclasts, derived from mesenchymal cells, are responsible for bone resorption, whereas osteoblasts, from hematopoietic precursors, are responsible for bone formation. The 2 types of cells are dependent on each other for production and linked in the process of bone remodeling
  10. 10.   In osteoporosis a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Under physiologic conditions, bone formation and resorption are in a fair balance. A change in either—that is, increased bone resorption or decreased bone formation may result in osteoporosis.
  11. 11.   Accelerated bone loss can be affected by hormonal status, as occurs in perimenopausal women Aging and loss of gonadal function are the 2 most important factors contributing to the development of osteoporosis
  12. 12.    Estrogen deficiency accelerates bone loss in postmenopausal women. Estrogen deficiency can lead to excessive bone resorption accompanied by inadequate bone formation. Osteoblasts, osteocytes, and osteoclasts all estrogen receptors.
  13. 13.   In the absence of estrogen, T cells promote osteoclast recruitment, and prolonged survival via IL-1, IL-6, and tumor necrosis factor (TNF)–alpha. With the prolonged osteoclast survival, rate of bone resorption will increase.
  14. 14.   In contrast to postmenopausal bone loss, which is associated with excessive osteoclast activity, the bone loss that accompanies aging is associated with a progressive decline in the supply of osteoblasts in proportion to the demand. After the third decade of life, bone resorption exceeds bone formation
  15. 15.  Calcium and vitamin D help maintain bone homeostasis. Insufficient dietary calcium or impaired intestinal absorption of calcium can lead to secondary hyperparathyroidism. PTH is secreted in response to low serum calcium levels. It increases calcium resorption from bone, decreases renal calcium excretion, and increases renal production of 1,25dihydroxyvitamin D (1,25[OH]2 D)—an active hormonal form of vitamin D that optimizes calcium and phosphorus absorption
  16. 16.  Medications that lead to bone loss (eg, glucocorticoids) can cause osteoporosis. Corticosteroids inhibit osteoblast function and enhance osteoblast apoptosis
  17. 17.  Primary Osteoporosis ◦ Postmenopausal osteoporosis.  Accelerated bone loss related to oestrogen deficiency ◦ Age-related osteoporosis. This occurs in both men and women ◦ Idiopathic (rare)
  18. 18.  Most patients are asymptomatic and diagnosis is made only after a fracture. Common clinical presentations include: ◦ ◦ ◦ ◦ Increasing dorsal kyphosis Low trauma fracture Loss of height Back pain
  19. 19.      a careful history, physical examination and appropriate laboratory investigations, is mandatory When a patient presents with a low trauma fracture, osteoporosis is a presumptive diagnosis. BMD (DXA) is advised. If absence of this facility, treatment should still be initiated. In the absence of a fragility fracture, the gold standard for the diagnosis of osteoporosis remains the measurement of BMD using DXA. If a BMD measurement is not available, calculating the risk of fractures using Fracture Risk Assessment Tool (FRAX) can help in deciding treatment strategies.
  20. 20.   FRAX is a fracture risk assessment tool used to evaluate the 10-year probability of hip and major osteoporotic fracture risk that integrates clinical risk factors and bone mineral density at the femoral neck in its calculations. Until more Malaysian data are available, it is recommended to use the Singapore prediction algorithm.
  21. 21.    A simple clinical screening tool, based on age and weight, Osteoporosis OSTA was developed for postmenopausal Asian women. Women in the high risk category and those in the moderate risk category with additional risk factors (e.g. glucocorticoid use, hypogonadism, immobilisation) for osteoporosis should be recommended for DXA
  22. 22. The main aims of investigations are to: 1. Confirm the diagnosis of osteoporosis 2. Assess fracture risk 3. Exclude secondary causes 
  23. 23.  Initial investigations include: 1. FBC, ESR 2. Bone profile: serum calcium, phosphate, albumin 3. Alkaline phosphatase 4. Renal function 5. Plain X-rays - lateral thoraco-lumbar spine or hip (as indicated)
  24. 24.  clinical suspicion of secondary causes: ◦ ◦ ◦ ◦ ◦ ◦ ◦ free thyroxine T4 (FT4), thyroid-stimulating hormone (TSH), testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), urine Bence Jones protein, serum protein electrophoresis]
  25. 25.  Densitometry ◦ BMD measurement gives an accurate reflection of bone mass and helps in establishing the diagnosis of osteoporosis ◦ use race-specific reference ranges when available ◦ results are reported as  T-scores (comparison with the young adult mean)  The risk of fracture is increased two fold for each SD reduction of T-score in BMD  Z-scores (comparison with the mean of individuals of the same age)
  26. 26.    gold standard for diagnosis measured at the hip and lumbar spine. Prediction of fracture risk is site-specific. ◦ If not available, other skeletal sites can be used to provide an adequate estimation of fracture risk.  Peripheral DXA (phalanges / distal radius / calcaneum)
  27. 27.   an alternative technique for measuring bone density in the axial skeleton and vertebral volumetric bone density The main limitations are the lack of availability in Malaysia and a higher radiation dose compared to DXA
  28. 28.     to identify patients at high risk of future fractures. They should not be used for the diagnosis of osteoporosis. used to evaluate treatment efficacy and compliance to therapy Changes in level of BTM can be seen within 3-6 months after initiation of drug therapy.
  29. 29.  The aim ::to assess the response to treatment. ◦ regular clinical assessments ◦ peripheral DXA is not recommended ◦ If biochemical markers are available, two separate baseline measurements of the same marker need to be carried out followed by one repeat measurement 2-3 months after initiating therapy and yearly thereafter, if indicated. These measurements should be taken at the same time of the day to minimise the effect of diurnal variation.
  30. 30.  Nutrition I. Calcium
  31. 31. II. Vitamin D ◦ >50 years old or older, the Malaysian Recommended Nutrient Intake advocates 400 IU of vitamin D per day, but many experts recommend at least 800 to 1000 IU per day
  32. 32.   Low body weight and excessive dieting is associated with low bone mineral status and increased fracture risk Maintenance of a BMI >19 kg/m 2 is recommended for prevention of osteoporosis
  33. 33.   Patients should be advised to limit their caffeine intake to less than 1 to 2 servings (240 to 360 mls in each serving) of caffeinated drinks per day. Caffeine intake leads to a slight decrease in intestinal calcium absorption and an increase in urinary calcium excretion
  34. 34.   Cigarette smoking increases osteoporotic fracture risk and thus should be avoided Excessive intake of alcohol should be avoided because alcohol has detrimental effects on fracture
  35. 35.  Regular physical activity, in particular weightbearing exercise ◦ (e.g. brisk walking, line dancing) is encouraged in all age groups in order to maximise peak bone mass, decrease age-related bone loss, maintain muscle strength and balance  The individual’s health status should be taken into consideration when recommending an exercise programme.
  36. 36. o Most osteoporosis-related fractures, especially in the elderly, are a consequence of decreased BMD and falls
  37. 37. I. Hormonal therapy (HT) HT is an effective treatment for menopausal symptoms that also offers good protection for bone. ₋ Estrogen Therapy (with or without progestin) increases lumbar spine BMD ◦ HT is not recommended in women with breast cancer, coronary heart disease or stroke. ⁻
  38. 38.  Bisphosphonates are potent inhibitors of bone resorption. ◦ Alendronate, risedronate, ibandronate, zoledronic acid ◦ Two adverse effects have been noted in bisphosphonate therapy:  Atypical femoral shaft fractures  Osteonecrosis of the jaw (ONJ) :exposed, non-vital bone involving maxillofacial structures, with delayed healing despite > 8 weeks of appropriate medical care
  39. 39. CKD Stages 1-3  Patients with CKD stages 1-3 and low Tscores or low trauma fractures, most likely have osteoporosis. Bisphosphonates can be used safely. CKD Stages 4-5  Bisphosphonates are not recommended for patients with an estimated GFR < 30 ml/min
  40. 40.   In established osteoporosis, calcium supplementation alone is not adequate for fracture prevention. However, calcium supplementation is necessary for optimal response to other treatment modalities
  41. 41.  Activated Vitamin D (calcitriol 0.25 μg bd, alfacalcidol 1 μg od) has been demonstrated to increase BMD in those with established osteoporosis1
  42. 42.   Calcitonin has also been shown to have an analgesic effect for acute pain in osteoporosis related vertebral fractures Side effects of calcitonin include nausea, flushing, vomiting and nasal irritation.
  43. 43. 1. 2. 3. 4. CPG - Management of Osteoporosis June 2012 Harrison's Principles of Internal Medicine, 18th ed www.m.webmd.com/a-to-z-guides/bonemineral-density-test. www.medscape.com/osteoporosis/overview .