Metabolic bone disease

1. METABOLIC BONE DISEASE
Dr. KAPIL DEV

2. Composition of Bone
The extracellular matrix
40% organic
 Type 1 collagen
Proteoglycan
Osteocalcin/osteonectin
Growth factors/cytokines
 60% inorganic
Calcium hydroxyapatite Ca10(PO4)6(OH)2
The cells
Osteo-clast/blast/cytes/progenitors

3. Bone Turn over

4. Calcium metabolism
 What is recommended daily intake?
 Adult:1000 mg/day
 Pregnancy,lactation,postmenopausal:1.3g/day
 Children (1-18 yrs):0.5-1.3 g/day
 Infant (<1 yr):300-500 mg/day
 What is plasma concentration?
 Total (mg/dL): 8.6-10.3
(mmol/L): 2.15-2.57
 Ionized (mg/dL): 4.5-5.6
(mmol/L): 1.1-1.4
Ref: Harrison’s 18th edition

6. Phosphate Metabolism
 What is recommended daily intake?
Infants (< 1yrs): 100-275 mg/day
Children (1-18 yrs): 460-1250 mg/day
Adults:700-1250 mg/day
Pregnancy/lactation: 700-1250 mg/day
 What is plasma concentration?
Adult:2.5-4.5 mg/dL
Children:4-7 mg/dL
Ref: Harrison’s 18th edition

8. Parathyroid hormone (PTH)
• Synthesizes and secreted by chief cells of
parathyroid gland
• Synthesized as pre-pro-PTH, cleaved
enzymatically to intact PTH
• Plasma calcium: primary physiological
regulator of PTH synthesis and secretion
• Normal Reference Range: 10 -65 ng/L

9. Effect on serum levels: increase Ca, decrease P
Target organ Action
Kidney Increase reabsorption of Ca
Increase excretion of P
Bone Increase Ca/P mobilization
from bone
GIT Increase in Ca absorption
by stimulating activation of
Vitamin D

10. Vitamin D
• Sources of vitamin D?
Diet
UV light exposure on precursor in skin
• Daily requirement?
400 International units

11. Target organ Action
Bone Increase Ca mobilisation from bone
GIT Increase in Ca absorption
Effect on serum levels: increase Ca, decrease P

12. Calcitonin
• Secreted by parafollicular or C cells
distributed throughout thyroid gland
• Normal serum concentration
Men:<8.8 pg/mL
Women:<5.8 pg/mL
• Level Increases when serum Ca concentration
>2.25mmol/L
Ref: Harrison’s 18th edition

13. Effect on serum levels: decrease Ca, increase P
Target organ Action
Bone Supresses resorption
Kidney Increase excretion of Ca

14. Alkaline Phosphate
Present in all tissue, concentrated in liver,
intestins, kidney, bone and placenta
 Normal range: 20 – 140 IU/L

15. Recent Markers
Osteoblasts
Osteoid
Osteocyte
Bone matrix
Osteoclast
Markers of bone resorption (Urine)
Hydroxyproline
Collagen cross-links
Pyridinolines (pyridinoline,
deoxypyridinoline)
Cross-linked telopeptides (NTx, CTx)
Tartrate-Resistant Acid Posphate
Markers of bone formation (serum)
Bone alkaline phosphatase
Osteocalcin
Procollagen type I propeptides (PINP, PICP)

16. Disease with markers
Disease S. Ca S. PO4 S.PTH S. ALP Recent biomarker
Osteoporosis N N N N/high Cathepsin K
C- telopeptide
Rickets/Osetmalacia Low low high high Osteocalcin
Paget’s disease N N N high --------

17. Metabolic bone diseases
heterogeneous group of disorders characterized by abnormalities in
calciummetabolism and/or bone cell physiology. They lead to analtered serum
calcium concentration and/or skeletal failure. The most common type of metabolic
bone disease in developed countries is osteoporosis
• Osteoporosis
• Osteomalacia & Rickets
• Renal Osteodystrophy

18. Rickets & Osteomalacia
Rickets is defective mineralization of bones
before epiphysial closure in immature mammals
due to deficiency or impaired metabolism
of vitamin D, phosphorus or calcium ,potentially
leading to fractures and deformity.
Osteomalacia is a similar condition occurring in
adults, generally due to a deficiency of vitamin
D but occurs after epiphyseal closure.

19. Rickets & Osteomalacia
Vit D deficiency
low intake plus inadequate sunlight exposure
malabsorption
Abnormal vit D metabolism
Liver disease
Renal disease
Drugs(anticonvulsants)
Hypophosphatemia
Low intake
Hypophosphatemic Vitamin D resistant rickets(X-linked)

20. • Skeletal deformity
Toddlers: Bowed legs (genu varum)
Older children: Knock-knees (genu valgum) or
"windswept knees"
Cranial deformity (such as skull bossing or delayed
fontanelle closure)
Pelvic deformity
Spinal deformity (such as kyphoscoliosis or
lumbar lordosis)

26. Rickets & Osteomalacia
• Lab investigations include :
• S. ALP ↑
• Ca low in Vitamin D deficiency
• Phosphate may be normal or low
• PTH may ↑

27. OSTEOPOROSIS
Common in developed countries
Associated with advanced age
Associated with increased risk of fractures (hip,
vertebrae, forearm)
Exercise & nutrition play an important role in
attaining adequate skeletal mass
During early adult life bone formation = bone
resorption
Aging increases bone resorption

29. OSTEOPOROSIS
• Pathophysiology
 Inadequate bone formation during
growth
 Pathophysiological process
impairing osteoblastic bone
formation
 Increase in bone resorption

30. Factors involved in causation of
osteoporosis
Hormones
Poor diet
Genetic factors
Cytokines
Prostaglandins
Growth factors
Low physical activity and low exposure to
sunlight

31. Osteoporosis
• Risk Factors
- Early menopause
- family history
- Sedentary life
- Low calcium intake
- Cigarette smoking
- Excessive alcohol
- Excessive caffeine
- steroid therapy
- Most commonly
encountered in post
menopausal females

32. Clinical presentations
Back pain
Fractures
Investigations
Routine X-rays
Bone scan
Investigations for secondary causes

34. Osteoporosis (management)
 Exercise
 Calcium
 Vit D
 Bisphosponates
 Oestrogen replacement
 Androgens

35. Pagets Disease
Disease of bone remodelling
osteoclast mediated bone resorption followed by
new bone formation
Cause unknown ?virus (paramyxovirus)
More common in caucasian

36. Pagets Disease (clinical
manifestation)
Bone pain
Joint pain
Deformity
Spontaneous fractures

37. Pagets Disease (complications)
Fractures
Deafness
Nerve entrapment
Spinal stenosis
Cardiac failure
Osteogenic sarcoma
Hypercalcemia

38. Pagets Disease (investigations)
↑ markers of bone formation
↑ ↑ Serum alk phosphatase
Urinary hydroxy proline and pyridinoline cross links
X-rays
cortical thikening
osteolytic, & osteiosclerotic
 bone scan

39. RENAL OSTEODYSTROPHY
• Associated with CRF
a) ↓excretion of PO4 ---> ↑ PO4
b) Inability of kidney to synthesise 1,25 (OH)2D (↓ renal
mass & ↑ PO4)
c) ↓ intestinal absorption of Ca ---> hypocalcemia
• Results in hyper parathyroidism

41. RENAL OSTEODYSTROPHY : CLINICAL
MENIFESTATIONS
• BONE PAINS (WT BEARING)
• SKELETAL DEFORMITIES IN CHILD
• EXTRACELLULAR CALCIFICATION

42. • LAB INVESTIGATIONS:
 ↑ PO4
 HYPOCALCEMIA
 ↑ PTH
 ↓1,25 (OH)2 D
 ↑ ALP
 Mg ↑

44. THANK YOU