1. N.Movaffagh MD Rheumatologist
Osteoporosis
N.Movaffagh MD
Rheumatologist

2. DEFINITION Reduction in the strength of bone that
leads to an increased risk of fractures
WHO defines:
Bone density that falls 2.5 standard deviations (SD) below the mean for young healthy adults of the same sex

3. Osteoporosis T-score of<-2.5
low bone density T-score <–1.0

4. EPIDEMIOLOGY 9 million adults have osteoporosis(United States)
48 million individuals have low bone density
more frequently with increasing age as bone tissue is lost progressively

5. In women at menopause(typically about age 50) precipitates rapid bone loss

6. hip fracture : Asians=white > African Americans

7. In the United States and Europe:
osteoporosis-related fractures are more common among women than men
presumably due to a lower peak bone mass as well as postmenopausal bone loss in women

8. a fracture in a person over 50 should trigger evaluation for osteoporosis

9. Risk factors of Osteoporesis & Fractures
Lifestyle factors
Genetic factors
Hypogonadal states
Endocrine disorders
Gastrointestinal disorders
Hematologic disorders
Rheumatologic and autoimmune diseases
Central nervous system disorders
Medications

10. Lifestyle factors Low calcium intake
Vitamin D insufficiency, Alcohol abuse ,High salt intake
Excess vitamin A
Inadequate physical activity
Immobilization
Excessive thinness
Prior fractures
Smoking
Falling

11. Genetic factors Parental history of hip fracture Hemochromatosis
Marfan’s syndrome
Hypophosphatasia

12. Endocrine disorders Diabetes mellitus (types1 and 2)
Hyperparathyroidism
Thyrotoxicosis

13. Gastrointestinal disorders
Celiac disease
Inflammatory bowel disease
Pancreatic disease
Malabsorption

14. Medications Anticoagulants (heparin) Anticonvulsants Barbiturates
Lithium
Methotrexate
Glucocorticoids (≥5 mg/d prednisone or equivalent for ≥3 months)
Thyroid hormones (in excess)
Aluminum (in antacids)
Proton pump inhibitors

15. PATHOPHYSIOLOGY Bone Modeling During growth, the skeleton increases in
size by apposition of new bone tissue on the outer surfaces of the cortex
modeling, a process that also allows the long bones to adapt in shape to the stresses placed on them

16. Increased sex hormone production at
puberty is required for skeletal maturation
which reaches maximum mass and density in early adulthood

17. It is around puberty that the sexual dimorphism in skeletal size becomes obvious, although true bone density remains similar between the sexes

18. Important factors in growth:
sex hormone
Nutrition and lifestyle
genetic factors
genetic factors primarily determine peak skeletal mass and density

19. peak bone mass is often lower among individuals with a family history of osteoporosis

20. Genetic factors LRP5 low-density lipoprotein receptor–related protein
LRP5 signaling appears to be important
in controlling bone formation
LRP5 acts through the Wnt signaling pathway

21. With LRP5 and Wnt activation, beta-catenin is translocated to the nucleus
stimulation of osteoblast formation, activation, suppression of osteoclast activity
increasing bone formation
sclerostin, is a negative inhibitor of Wnt signaling

23. LRP5 Families with high bone mass
and without much apparent age-related
bone loss have been shown
to have a point mutation in LRP5

24. BONE REMODELING
In adults, bone remodeling, not modeling, is the principal metabolic skeletal process.
Two primary functions of bone remodeling:
(1) to repair microdamage within the skeleton to maintain skeletal strength and ensure the relative youth of the skeleton
(2) to supply calcium from the skeleton to maintain serum calcium

25. Bone remodeling is regulated by
Estrogens
Androgens
vitamin D
PTH
(PTH rP) PTH–related peptide
IGF-I
IGH-II (immunoreactive growth hormone II)
TGF-β
Ils
Prostaglandins
members of TNF

26. BONE REMODELING A process that results in :
Bone resorption by osteoclasts(initially)
New bone formation by osteoblasts(followe)

27. In young adults, resorbed bone is replaced by an equal amount of new bone tissue
Thus,mass of the skeleton remains constant after peak bone mass is achieved in adulthood
After age 30–45, the resorption and formation
processes become imbalanced and resorption exceeds formation
exaggerated in postmenopausal women

28. Modulation of osteoclast activity
RANKL (RANK ligand)
RANK (osteoclast receptor for RANKL)
Osteoprotegerin (OPG)
Nutrition (particularly calcium intake)
Physical activity level

30. Mechanism of bone remodeling
A. Origination of BMU-lining cells contracts to expose collagen and attract preosteoclasts
B. Osteoclasts fuse into multinucleated cells that resorb a cavity
Mononuclear cells continue resorption, and preosteoblasts,are stimulated to proliferate

31. C. Osteoblasts align at bottom of cavity and start forming osteoid
D. Osteoblasts continue formation and mineralization
Previous osteoid starts to mineralize
E. Osteoblasts begin to flatten
F. Osteoblasts turn into lining cells

34. CALCIUM NUTRITION
Peak bone mass may be impaired by inadequate calcium intake during
growth
leading to increased risk of osteoporosis later in life

35. During adult phase insufficient calcium
Relative secondary hyperparathyroidism
increase in the rate of bone remodeling to
maintain normal serum calcium levels

36. PTH stimulates
Production of 1,25-dihydroxyvitamin D [1,25(OH)2D]
calcium absorption of GI
reduces renal calcium loss

37. the long-term effects are detrimental to the skeleton
increased remodeling rates
imbalance between resorption and formation at remodeling sites

38. Total daily calcium intakes <400 mg are detrimental to the skeleton
recommended daily required intake of 1000–1200 mg for adults

39. VITAMIN D
vitamin D insufficiency may be more prevalent than previously

40. risk factors for vitamin D deficiency
Elderly
living in northern latitudes
poor nutrition
Malabsorption
chronic liver or renal disease
Dark-skinned individuals

41. optimal levels of serum [25(OH)D]: >20 or 30 ng/mL
daily vit D intakes: 800–1000 units/d

42. Vitamin D insufficiency leads:
secondary hyperparathyroidism
an important risk factor for op and fractures

43. Treatment with vitamin D result in:
Prevent of increase in bone remodeling, bone loss and fractures
Improved muscle function and gait

44. Vitamin D adequacy also may affect:
Risk and/or severity of other diseases including:
cancers (colorectal, prostate, breast)
autoimmune diseases
diabetes

45. ESTROGEN STATUS Estrogen deficiency probably causes bone loss
Mechanisms:
(1) activation of new bone remodeling sites
(2) exaggeration of the imbalance between bone formation and resorption

46. most common estrogen-deficient state:
cessation of ovarian function at the time of menopause(age 51)

47. causes bone loss due to estrogen deficiency:
Marrow cells (macrophages, monocytes, osteoclast precursors, mast cells)&bone cells (osteoblasts, osteocytes,osteoclasts) express ERs α and β

48. RANKL &
estrogen OPG &
Osteoclast recruitment

49. Estrogen controlling the rate of bone cells apoptosis

50. Estrogen deficiency affected trabecular bone
than cortical bone
vertebral fractures are the most common early consequence of estrogen deficiency

51. PHYSICAL ACTIVITY Inactivity, results in significant bone loss
These changes in skeletal mass are most marked when the stimulus begins during growth and before the age of puberty

52. MEDICATIONS Glucocorticoids
most common cause of medication-induced osteoporosis
Excessive doses of thyroid hormone
Anticonvulsants
Some anticonvulsants induce the cytochrome P450 system and vitamin D metabolism
proton pump inhibitors

53. CIGARETTE CONSUMPTION
Effects:
directly by toxic effects on osteoblasts
indirectly by modifying estrogen metabolism
produces secondary effects that can modulate skeletal status
(decreased exercise, poor nutrition)

54. MEASUREMENT OF BONE MASS
techniques for estimating skeletal mass or density:
dual-energy x-ray absorptiometry(DXA)
quantitative CT
ultrasound (US)

55. T-scores (a T-score of 1 equals 1 SD), which compare individual results to those in a young
population that is matched for race and sex.

56. Z-scores (measured in SD) compare individual results to those of an age-matched population
&matched for race and sex

57. a 60-year-old woman with a Z-score of –1 (1 SD below mean for age) has a T-score of –2.5 (2.5 SD below mean for a young control group)

58. Relationship between Z-scores and T-scores in a 60-year-old woman.

59. screening vertebral imaging is recommended in women and men with low bone mass
(T-score <1) by age 70 and 80, respectively

60. Indications for Bone Density Testing
Women age 65 and older and men age 70 and older, regardless of clinical risk factors
Younger postmenopausal women, women in the menopausal transition and men age 50–69 with clinical risk factors for fracture
Adults who have a fracture after age 50
• Adults with a condition (e.g., rheumatoid arthritis) or taking a medication(e.g., glucocorticoids)
in a daily dose ≥5 mg prednisone or equivalent for≥3 months) associated with low bone mass or bone loss

61. TREAT BASED ON BONE MASS RESULTS
BMD is >2.5 SD below the mean value for young adults (T-score ≤–2.5)
in either spine, total hip, or femoral neck

62. APPROACH TO THE PATIENT
history and physical examination
to identify risk factors for osteoporosis
A low Z-score increases the suspicion of a secondary disease
R/O malignancy in fractures

63. APPROACH TO THE PATIENT
indication for VFA by DXA or radiography:
Height loss >2.5–3.8 cm
significant kyphosis
back pain

64. ROUTINE LABORATORY EVALUATION
Complete blood count
serum and 24-h urine calcium
25(OH)D level
Renal and hepatic function tests
TSH

65. urine calcium(<50 mg/24 h) suggests osteomalacia, malnutrition, or malabsorption
urine calcium (>300 mg/24 h) is indicative of hypercalciuria
suggests hematologic malignancies, hyperparathyroidism, and hyperthyroidism
25(OH)D level, achieves to a target level >20–30 ng/mL

66. Lab Data Urinary free cortisol levels serum albumin, cholesterol
antigliadin,antiendomysial,transglutaminase antibodies
Serum and urine proteins electrophoresis
using 24-h urine histamine or serum tryptase
bone marrow biopsy

67. BIOCHEMICAL MARKERS
related primarily to bone formation or bone resorption
help in the prediction of fracture risk
Monitoring the response to treatment
C-telopeptide [CTX ]
before initiating therapy and 3–6 months after
starting therapy provides an earlier estimate of
patient response than does bone densitometry.

68. TREATMENT MANAGEMENT OF PATIENTS WITH FRACTURES
Hip fractures surgical repair
vertebral, rib, and pelvic fractures usually are managed with supportive care
Analgesics
calcitonin may reduce pain related to acute vertebral compression fracture
Short periods of bed rest
muscle relaxants ,heat treatments

69. TREATMENT MANAGEMENT OF THE UNDERLYING DISEASE Risk Factor Reduction
Several tools exist for risk assessment
most commonly available is the FRAX tool

71. FRAX
10-year major fracture risk (including hip, spine, proximal humerus, and tibia) from FRAX is ≥20%
10-year risk of hip fracture is ≥3%
treat patient

72. Treatment Nutrition Exercise PHARMACOLOGIC THERAPIES: Estrogens
SERMs: raloxifene
Bisphosphonates: Alendronate