METABOLIC BONE DS

1. METABOLIC BONE
DISEASES
PRESENTER
DR. MANASIL MALLA, JR1
DEPARTMENT OF ORTHOPAEDICS
KATHMANDU MEDICAL COLLEGE TEACHING HOSPITAL
SINAMANGAL

2. METABOLIC BONE DISEASE
• OSTEOPOROSIS
• RICKETS/OSTEOMALACIA
• PAGETS DISEASE
• HYPERPARATHYROIDISM

3. OSTEOPOROSIS

4. OSTEOPOROSIS
• Osteo means “bone” and porosis means
“porous”

5. • Abnormally low bone mass with defects in bone structure
leading to
• Fragile
• greater than normal risk of fracture

6. WHO definition
Bone Mineral Density (BMD) that lies 2.5 SD or more below the
average value for young healthy adult of same sex and race
(T score <-2.5 )
CLASSIFICATION T- SCORE
NORMAL
-1 AND ABOVE
OSTEOPENIA
-2.5 TO -1
OSTEOPOROSIS
LESS THAN -2.5

7. EPIDEMIOLOGY
• 200 million people worldwide have osteoporosis
• In Nepal, prevalence of osteoporosis 22.4%

8. DEMOGRAPHICS
• Male : Female ratio is 1:4
Low Peak Bone Mass
Hormonal changes after menopause
• Men have a higher prevalence of secondary
osteoporosis

9. Vertebral fractures > Hip Fractures > Colles Fractures

10. TYPES OF OSTEOPOROSIS
PRIMARY SECONDARY
Type I :
(POST MENOPAUSAL )
• Estrogen Withdrawal Effect
• Almost exclusively trabecular
Type II :
(SENILE )
• Age Related >70 years
• Trabecular > Cortical bone
SYSTEMIC DISEASES :
 Hyperthyroidism
 Skeletal Metastases
 Multiple Myeloma
DRUGS :
 Corticosteroids
 Anticonvulsants
LIFESTYLE :
 Alcohol
 Smoking

11. Systemic Diseases Causing
Osteoporosis
Endocrinal Disorders :
 Cushing’s Syndrome
 Hyperparathyroidism
 Thyrotoxicosis
 Diabetes
 Adrenal Insufficiency
Rheumatological
Disorders :
 Rheumatoid Arthritis
 Ankylosing Spondylitis
Inherited Disorders
 Osteogenesis
Imperfecta
 Marfans Syndrome
Nutritional/ GI
disorders
 Malabsorption
Syndromes
 Chronic Liver Disease
 Pernicious anemia

12. Systemic Diseases Causing
Osteoporosis
Hypogonadal States
 Turners Syndrome
 Kleinfelters Syndrome
Hematological Disorders
 Multiple Myeloma
 Leukemia
 Lymphoma

13. DRUGS THAT CAUSE
OSTEOPOROSIS
 Glucocorticoids
 Cyclospoprine
 Anticonvulsant Drugs
 Aromatase Inhibitors
 SSRIs
 Proton Pump Inhibitors
 Lithium
 OHA (Thiazolidinediones)
 Excessive Thyroxine

14. Risk Factors
Modifiable Risk Factors
 Inadequate nutritional
absorption
 Lack of physical activity
 Underweight
 (BMI < 18.5 kg/m2 )
 Cigarette Smoking
 Alcohol Consumption
 >14U/wk in women
 >21U/wk in men
 Vitamin D Deficiency

15. Risk Factors
Non-modifiable Risk Factors
Advancing age
Sex (postmenopausal
women)
Asian race
Previous hip fractures
Family history of
osteoporosis
Rheumatoid arthritis

16. PATHOPHYSIOLOGY
Bone Formation
Bone Resorption
Imbalance between Bone Formation and Bone Resorption

17. • In young adults:
– Resorbed bone replaced by equal amount of new
bone tissue
• After age 30–45:
– resorption slowly exceeds formation (exaggerated in
postmenopausal women)

18. • Loss of estrogen
– increases production of Receptor Activator of Nuclear
Factor-ќβ Ligand (RANKL)
– Decreased production of osteoprotegerin
increases osteoclast activation and resorption

19. CLINICAL FEATURES
SYMPTOMS
Mostly asymptomatic
Back pain
Back deformity

20. Signs
Dowagers/ Widows hump
Loss of height
Point tenderness without
neurological symptoms
Multiple fractures thoracic
kyphosis and Loss of height

21. XRAYS
• 1st Investigation
• Not Diagnostic
• Radiological osteopenia :
 Bone which appears to be less ‘dense’ than
normal on X-ray

22. • Typical signs of radiological
osteopenia :
– Loss of trabecular definition
– Thinning of the cortices
– Compression fractures of the
vertebral bodies (wedging
or compression of the vertebral
end plates)
– Codfish vertebra

23. SINGH’S INDEX
Developed by Dr. Manmohan Singh (1970, JBJS)
Classified Xrays of Hip
Based on the visibility of the trabecular types seen in
the femoral neck
As osteoporosis progresses these trabeculae get
thinner and eventually disappear

24. Five trabecular types can be present in the proximal
part of the femur:
1. principal compression
2. secondary compression
3. primary tensile
4. secondary tensile
5. intertrochanteric

25. GRADE 6
All normal trabeculae groups visible

26. GRADE 5
Loss of trochanteric and secondary trabeculae

27. GRADE 4
• Reduced but continuous primary tensile group

28. GRADE 3
• Discontinuous primary tensile group

29. GRADE 2
Loss of primary tensile group

30. GRADE 1
• Reduction in primary compressive group

31. LAB INVESTIGATIONS
DIAGNOSIS Investigate Secondary
Causes
 Dual Energy Xray
Absorptiometry (DEXA)
Scan
(Gold Standard )
Others: (FDA Approved)
 Quantitative CT
 Quantitative Ultrasound
 Liver Function Tests
 Renal Function Tests
 Thyroid Function Tests
 Serum Vitamin D
 Serum / 24 Hr Urine Calcium
 Urine Bence jones protein
/Bone Biopsy

32. Indications for BMD measurement
(The International Society for Clinical
Densitometry)
• Women ≥ 65 years and Men ≥ 70 years
• Adults > 50 years with Risk Factors
• Adults with fragility fracture
• Anyone being considered for pharmacological
therapy for osteoporosis

33. DEXA
Dual Energy Xray Absorptiometry
• GOLD Standard for
measuring BMD
• High Accuracy
• Sites to be examined in
DEXA :
 Femoral Neck
 Lumbar Spine

34. DEXA
• 2 photons with different
attenuation profiles
produced
• Patient positioning
• The more dense the bones
(from greater mineral
content), the more energy
is absorbed, and the less
energy detected

36. DEXA
Advantages
 High Accuracy
 Low Radiation Dose to
patient
 Very little Scatter
Radiation to Technician
 Takes only about 20 min
Limitations
Cant differentiate Cortical
or Trabecular Bone
Bone spurs (OA) falsely
increase bone density

37. Quantitative CT
• Measures precise Volumetric bone mineral density
• Separate BMD measurement for Trabecular and cortical bone
• Sensitivity of upto 85% and a specificity of 89%
• The detection rate for osteoporosis was 10.9% for DEXA and 45.1% for
QCT, a statistically significant difference

38. Quantitative CT
Advantages
 Geometry of bone (
spatial distribution of
bone mass )
Bone Density + Bone mass
Existing previous CT can
be used
Limitations
High Radiation dose
Expensive

39. Fracture Risk Assessment Tool
FRAX®
Developed by WHO
Predicts 10 year probability of
major osteoporotic fractures
Hip, vertebrae, humerus, wrist

40. Non Pharmacological Treatments :
• Exercise
– Both resistance and balance training
– Prevents bone loss but no gain of bone mass

41. Non Pharmacological Treatments :
Diet Rich in Calcium and Vitamins
Dairy products
Ground Nut
Soyabeans
Sardines

42. Dietary Supplements
• Calcium and Vitamin D
Calcium combined with vitamin D leads to ∼20–
30% fracture risk reduction
With adequate Calcium intake  greater BMD
response to antiresorptive therapy

43. Pharmacological Therapy :
Prevention Treatment
ESTROGEN CALCITONIN
TERIPARATIDE
DENOSUMAB
BISPHOSPHONATES
 Alendronate
 Zolendronic Acid
 Ibandronate
 Risedronate

44.  DOC for osteoporosis treatment
 Reduce the incidence of
new vertebral fractures by up to 50%
hip fractures by 40%
BISPHOSPHONATES

45. DRUG DOSE ROUTE FREQUENCY
Alendronate 10 mg daily or 70
mg once weekly
ORAL ONCE DAILY /
WEEKLY
Risedronate 5 mg daily or 35 mg
weekly
ORAL ONCE DAILY OR
WEEKLY
Ibandronate 150 mg monthly ORAL / I.V ONCE A MONTH
ORALLY/ ONCE
EVERY 3 MONTHS
I.V
Zoledronic
acid
5 mg
(pre and post
Hydration )
I.V INFUSION ONCE A YEAR

46. Alendronate
Risedronate
Ibandronate
Zoledronic acid
Approved for the prevention
and treatment of
POSTMENOPAUSAL
OSTEOPOROSIS
 Alendronate
 Risedronate
 Zoledronic acid
Approved for the prevention
and treatment of
GLUCOCORTICOID
INDUCED OSTEOPOROSIS

47. MECHANISM OF ACTION
• Inhibit Osteoclast
• Alendronate : Inhibiting ATP in osteoclasts 
Apoptosis of Osteoclasts

48. • Risedronate/ Zolendronate :
Inhibit Mevalonate pathway (cholesterol
synthesis )  enzyme farnesyl pyrophosphate
synthase  no maturation of Osteoclasts 
Apoptosis of Osteoclasts

49. Precautions
(Oral Bisphosphonates)
1. Empty Stomach (reflux with food )
2. Full glass of Water (Dilute)
3. Donot lie down till 30 min (gastric emptying )

50. Side Effects
• Osteonecrosis of the jaw
• Atypical femoral fracture (Subtrochanteric
Fracture )

51. Denosumab
Monoclonal Antibody
Approved by the FDA in 2010
Given Subcutaneously
Every 6 months

52. MECHANISM OF ACTION
• Fully human monoclonal antibody to RANKL
• Binds to RANKL, inhibiting its ability to initiate
formation of mature osteoclasts from
osteoclast

53. Side effects
Hypersensitivity reactions
Hypocalcemia
Skin reactions including dermatitis
Rash and eczema
When denosumab is discontinued, there is a rebound increase in
bone turnover and acceleration of bone loss.

54. TERIPARATIDE
PTH ANALOGUE
PTH 1-34
Full Molecule of PTH is 84 AA  Osteoclastic
Pth 1-34  Osteoblastic
20 mcg S/C daily
Only drug that improves Bone Architecture (Both Trabecular and
Cortical )

55. SURGICAL TREATMENT GOALS
We are not just treating the fracture
Elderly patient with several comorbidities
Hollistic treatment

56. Use of Biological fixation
Use of Load Sharing Devices than Load bearing
device
Use of Wide Buttress Plates
Longer Nails and Plates
Use of Locking Screws
Augmentation by Bone cement or Bone grafts

57. • According to WHO, can a person travelling
from one country to another for a week be
labelled as having osteoporosis or not in
different countries ?

58. Osteoporosis and Orthopaedic
Surgery
In Cancellous Bone :
• Trabeculae are thinned and reduced in
number
• Thereby bone holding capacity of implant is
reduced

59. • In Cortical Bone :
• There is cortical thinning
(Endosteal thinning>
Periosteal bone formation)
• When a screw is fixed ,
instead of 4-5 threads , only
2 threads are engaged 
loosening of screws
Normal
Cortical
Thickness
Reduced
Cortical
Thickness

60. 20 years 80 years

61. RICKETS AND OSTEOMALACIA
• Different expressions of the same disease
• Inadequate mineralization of bone in children
is called rickets; in adults it is known as
osteomalacia
• Reduced serum 1,25-OHD is the most
common cause

62. Osteoporosis Osteomalacia
Definition
Reduced bone mass,
normal mineralization
Bone mass variable,
reduced mineralization
Age
Postmenopausal (Type I) or
elderly (Type II)
Any age
Etiology
Endocrine abnormality, age,
idiopathic, inactivity, alcohol,
calcium deficiency
Vit D deficiency,
hypophosphatemia, renal tubular
acidosis
Symptoms and signs
Pain and tenderness at
fracture site
Generalized bone pain and
tenderness
Xray Axial fracture predominance
Appendicular
fracture predominance,
Serum Ca Normal Low or normal
Serum PO4 Normal Low or normal
ALP Normal Elevated

63. ETIOLOGY
• VITAMIN D DEPENDENT FORMS (MOST
COMMON )
• VITAMIN D INDEPENDENT FORMS

64. VITAMIN DEPENDENT FORMS
Vitamin D deficiency
Reduced exposure to UV radiation
Low dietary intake
Decreased intestinal absorption
Impaired Vitamin D metabolism
 Impaired organ function (Liver cirrhosis/
Renal failure )
 Drugs: cytochrome P450 inducers
(Anticonvulsants, Rifampicin)
(increases the metabolism of vitamin D)

65. Impaired Vitamin D metabolism
Impaired organ function (Liver cirrhosis/ Renal
failure )
Drugs: cytochrome P450 inducers increase the
metabolism of vitamin D (Anticonvulsants,
Rifampicin)

66. • Vitamin D-independent forms (rare)
Renal tubular defects
Phosphate deficiency

67. CLINICAL FEATURES
(RICKETS )
• Tetany or convulsions (due
to hypocalcaemia)
• Failure to thrive
• Listlessness
• Muscular flaccidity
SYMPTOMS

68. • Craniotabes
• Rachitic rosary
• Harrison’s sulcus
• Lower limb deformities such as
– Coxa vara
– Bowing of the femur and tibia may
develop after weight-bearing
• Deformities of knee ( Genu Varum )
• Overall growth may be stunted
SIGNS

69. CLINICAL FEATURES
(OSTEOMALACIA)
• Insidious course
• Widespread bone pain / Stress
fracture
• Muscle weakness
– proximal distribution, causing a
‘waddling’ gait.
SYMPTOMS

70. • Waddling gait
• Tenderness over long
bones
SIGNS

71.  Thickening and widening of the growth
plate
 Cupping of the metaphysis
 Bowing of the diaphysis
 Widening of metaphysis
 Signs of secondary hyperparathyroidism:
subperiosteal erosions at the sites of
maximal remodelling
X-RAYS
(RICKETS)

72. XRAYS
(OSTEOMALACIA)
• The classical lesion of osteomalacia is the ‘Looser zone’
– a thin transverse band of rarefaction in an otherwise normal-looking bone
• Pubic rami, Medial proximal femur and axillary edge of the scapula
– (due to incomplete stress fractures which heal with callus lacking in calcium)
• Vertebral fractures  characteristic biconcave appearance or wedge
shaped deformities (indistinguishable from osteoporotic fractures)

73. Indentation of the acetabula producing the trefoil
or champagne glass pelvis

74. LAB PARAMETERS
• ↓ Calcium and ↓ phosphate
• ↑ Alkaline phosphatase and ↑ PTH
• Low 25-OHD level (typically < 10 nmol/L).

75. TREATMENT
• Vitamin D deficiency :
– administration of vitamin D
– Also indicated in infants who are exclusively breastfed
– adequate daily intake of calcium
• Defective vitamin D metabolism or vitamin D-independent
forms
– treatment of underlying disease

76. Pagets Disease
Localized sites of increased bone turnover
Enlargement and thickening of the bone
Internal architecture is abnormal
Unusually brittle bone

77. Pathophysiology
• Starts At Metaphysis To Involve Diaphysis
• Marked Increase In Osteoblastic And
Osteoclastic Activity
• Accelerated Bone Turnover

78. • Osteolytic Or Vascular Stage
– Large Resorption Filled With Vascular Fibrous Tissues
– Adjacent Area Osteoblastic Activity
– Involves Both Periosteum And Endosteum
– Increased Bone Thickness
• Osteoblastic Stage
– Thickened Bone Becomes Increasingly Sclerotic And
Brittle

79. Clinical Features
Symptoms
• Age Group : >50yrs of age
• Sex : M=F
• Sites : Pelvis and Tibia
– Femur, skull, clavicle and spine
• Mostly asymptomatic
• If symptomatic dull aching pain

80. Signs
• Deformity
– Anterior Tibial Bow
– Anterolateral Femoral Bow
• Osteitis Deformans
– Bent Limb, Thick Bone, Warm Skin
• Skull Base Thickening
– Short Neck
– Cranial Nerve Compression
• Steal Syndrome
• Spinal Claudication

81. Xray
• Flame Shaped Osteolytic Areas
• Osteoporosis Circumscripta
• Thick Sclerotic Bone With Coarse
Trabeculation

82. LAB PARAMETERS
• Serum Calcium And Phosphate Normal
• Raised ALP (Reflects Osteoblastic Activity)

83. Complications
• Fracture
• Osteoarthritis
• Nerve compression and Spinal stenosis
• High Output Cardiac failure
• Hypercalcemia
• Intraop bleeding
• Bone sarcoma

84. Treatment
• Non-Surgical :
– IV Zoledronate
• Surgical
– Fracture Fixation
– Arthroplasty For Severe And Painful Osteoarthritis
– Decompression For Nerve Entrapment And Canal Stenosis

86. Hyperparathyroidism
• Excess secretion of parathyroid hormone
• Cause
– Primary : Adenoma/Hyperplasia
– Secondary : Persistent Hypocalcemia
– Tertiary:

87. Primary Hyperthyroidism
• Solitary Adenoma
• 40-60 yrs
• Women: Men 2:1
• Asymptomatic
• Unexpectedly high Ca in routine examination

88. Effect of High PTH
• Tubular resorption
• Interstitial absorption
• Bone resorption

89. Clinical Feature
• Calcinosis , Stone formation Recurrent UTI
Calcification of soft tissue
• Loss of bone substance
• Subperiosteal erosion, endostoeal cavitation,
• Osteitis Fibrosa cystica
• Hemorrhage and giant cell reaction

90. Xray

91. • Rugger Jersey sign
• Salt pepper sign
• Brown Tumor

92. LAB PARAMETERS
• Hypercalcaemia
• Hypophosphataemia
• Serum PTH Concentration Raised
• Serum Alkaline Phosphatase Is Raised

93. Treatment
• Conservative
• Adequate Hydration And Decreased
Calcium Intake
• Indications For Parathyroidectomy
– Marked And Unremitting Hypercalcaemia,
– Recurrent Renal Calculi,
– Progressive Nephrocalcinosis
– Severe Osteoporosis.

94. Reference
• Apley & Solomon's System of Orthopaedics and
Trauma – 10e
• Harrison Principle of Internal medicine 21e
• Review article : Diagnosis and Treatment of
Osteoporosis: What Orthopaedic Surgeons Need to
Know
– Journal of the American Academy of Orthopaedic Surgeons
2019
• Review article : Diagnosis and Treatment of
Osteoporosis
– Institute for Clinical Systems Improvement / European
Journal of Rheumatology 2017