This document discusses metabolic bone diseases, including their composition, calcium and phosphate metabolism, and specific diseases. It provides details on osteoporosis, rickets/osteomalacia, Paget's disease, and renal osteodystrophy. The composition of bone includes collagen, proteoglycans, and hydroxyapatite. Calcium and vitamin D intake recommendations are outlined for different populations. PTH, calcitonin, vitamin D, and alkaline phosphatase roles in calcium regulation are summarized. Osteoporosis risk factors and management strategies are highlighted.

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