This document summarizes several metabolic bone diseases. It begins by describing bone composition and cells. It then discusses calcium, phosphate, parathyroid hormone, vitamin D, calcitonin, and alkaline phosphatase metabolism. Several metabolic bone diseases are covered in detail, including rickets/osteomalacia, osteoporosis, Paget's disease, and renal osteodystrophy. For each disease, causes, clinical presentations, investigations, and management are summarized.

1. METABOLIC BONE DISEASE

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. Calciton
in
• 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
Osteoblast
s
Osteoi
d
Osteocyt
e
Bone matrix
Osteocla
st
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. OSTEOPOR
OSIS
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. OSTEOPOR
OSIS
• 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. Osteoporo
sis
• Risk Factors
- Early
menopause
- family history
- Sedentary life
- Low calcium
intake
- Cigarette
smoking
- Excessive
alcohol
- Excessive
- 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. THANKY
O
U