This document summarizes key aspects of bone molecular biology and blood supply. It describes bone as a calcified connective tissue composed of inorganic hydroxyapatite and organic collagen. Bone cells include osteoblasts that form new bone, osteoclasts that resorb bone, and osteocytes embedded in the bone matrix. Bone is either compact cortical bone or spongy cancellous bone. The document also outlines the three sources of blood supply to bone from nutrient arteries, metaphyseal arteries, and the periosteal system which surrounds bone. Bone turnover is regulated through markers of bone formation by osteoblasts and resorption by osteoclasts.

1. Molecular Biology of bone and
blood supply
Dr. Ishdeep Singh Oberoi(PG-1)
Department of Orthopedics, SMS&R

2. WHAT IS A BONE?
BONE IS A SPECIALIZED CT WITH CALCIFIED INTRACELLULAR
SUBSTANCE.
IT PROVIDES
⇒ SKELETAL SUPPORT TO THE BODY
⇒ STORAGE OF CALCIUM + PHOSPHATE
⇒ PROTECTION OF INTERNAL STRUCTURES.
⇒ MANUFACTURING OF BLOOD ELEMENTS.
“the greater part of the tissue is
composed of intercellular substance, in
which, at certain intervals cells are
embedded” -Virchow

3. MOLECULAR
CLASSIFICATION OF BONE
Organic 30% Inorganic 70%
Hydroxyapatite
95% Ca5 (PO4) 3 (OH)
5% trace minerals
F, Cl, K, Mg, Mn, Na
Cells 2%
Osteoblasts
Osteoclasts
Osteocytes
Matrix 98 %
Collagen type 1 (90%)
Non collagenous ECM
Proteoglycans

4. BONE TISSUE
EXAMINATION OF THE CUT SURFACE OF A BONE
SHOWS THAT THE TISSUE ASSUMES TWO FORMS:
1. THE OUTER CORTICAL / COMPACT BONE
2. THE INNER CANCELLOUS / TRABECULAR BONE

5. CORTICAL BONE :
COMPACT BONE
CONTRIBUTES 80% OF BONE MASS
PREDOMINANT: SHAFT OF LONG BONES
HAVERSIAN SYSTEM PRESENT
POROSITY 10-15%
METABOLIC ACTIVITY LOW

6. CANCELLOUS BONE:
SPONGY BONE
CONTRIBUTES 20% BONE MASS
PREDOMINANT: ENDS OF LONG BONES +
VERTEBRA
POROSITY 30-90%
HAVERSIAN SYSTEM ABSENT
METABOLIC ACTIVITY HIGH

7. MINERALIZED BONE EXISTS IN TWO FORMS:
-WOVEN (IMMATURE, FIBER, OR PRIMARY) BONE
-LAMELLAR (MATURE, SECONDARY) BONE.

8. WB : WEAKER + MORE FLEXIBLE
EMBRYONIC SKELETON + METAPHYSEAL PARTS OF GROWTH PLATES.
-1ST BONE FORMED IN MANY HEALING FRACTURES AT ANY AGE
-HIGH RATE OF TURNOVER
-IRREGULAR, ALMOST RANDOM
-APPROXIMATELY FOUR TIMES AS MANY OSTEOCYTES / UNIT VOLUME
OF LAMELLAR BONE

9. LB: SECONDARY BONE CREATED BY REMODELING WOVEN BONE
STRONG + LESS FLEXIBLE
● COLLAGEN FIBRILS VARY LESS IN DIAMETER
● LIE IN TIGHTLY ALIGNED PARALLEL SHEETS FORMING DISTINCT
ALMOST UNIFORM DISTRIBUTION OF MINERAL THROUGHOUT THE
MATRIX.

10. Cells of bone tissue
1. OSTEOPROGENITOR CELLS
2. OSTEOBLASTS
3. OSTEOCLASTS
4. OSTEOCYTES

11. UNDIFFERENTIATED OR
OSTEOPROGENITOR CELLS
● SMALL CELLS WITH SINGLE NUCLEI, FEW ORGANELLES,
AND IRREGULAR FORMS
● REMAIN IN AN UNDIFFERENTIATED STATE UNTIL STIMULATED TO
PROLIFERATE OR DIFFERENTIATE INTO OSTEOBLASTS.
● THEY USUALLY RESIDE IN THE CANALS OF BONE, THE
ENDOSTEUM, AND THE PERIOSTEUM

12. OSTEOBLASTS
● MAKES BONE, DERIVED MESENCHYMAL LINEAGE
● CBFA1 RUNX2 - TFACTORS
● WNT PATHWAY STIMULATE, SCLEROSTIN -| TO WNT
● CUBOIDAL CELLS W SINGLE USUALLY ECCENTRIC NUCLEUS
● CONTAIN LARGE VOLUMES OF SYNTHETIC ORGANELLES(ER + GB)
● LIE ON BONE SURFACES
● FORM NEW BONE ORGANIC MATRIX AND PARTICIPATE IN CONTROLLING
MATRIX MINERALIZATION.
● LIFE SPAN VARIES, DAYS - WB, WEEKS - LB, YRS OSTEOBLAST-
>OSTEOCYTE

13. CBFA1
RUNX2

14. OSTEOCLAST
1, DERIVED-MONOCYTES, FUSE N FORM MULTINUCLEATED OC
RANK L : RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA-Β LIGAND
2. PTH RECEPTOR ON OSTEOBLAST BINDS TO PTH, LEADS TO EXPRESSION OF RANK L
RANK L BINDS RECEPTOR, LEADS TO RESORPTION
3. OPG(OSTEOPROTOGERIN) PRODUCED BY OSTEOBLASTS, BIND TO RANKL
INHIBITS OSTEOCLAST DIFFR AND ACTIVATION
4. HOWSHIP LACUNAE

16. OSTEOCYTES
● MATURE BONE CELL
● LIE IN A SMALL SPACE - LACUNAE
● THEY ARE CONNECTED WITH OTHER OSTEOCYTES BY THIN PROCESS
CALLED CANALICULI, USE TO EXCHANGE NUTRIENT WITH THE BLOOD
● MOST ABUNDANT & LONG LIVED CELLS
● THEY MAINTAIN THE BONE MATRIX

17. BONE TURNOVER MARKERS - RECENT ADVANCEMENT
BONE MINERAL DENSITY (BMD) ASSESSMENT USING DUAL-ENERGY X-RAY
ABSORPTIOMETRY (DXA) SCAN IS THE CURRENT GOLD STANDARD TEST FOR THE
DIAGNOSIS OF OSTEOPOROSIS.
STATIC AND EXPENSIVE INVESTIGATION
LIMITED AVAILABILITY IN THE MANY PARTS OF INDIA.
WIDER AVAILABILITY OF RELIABLE, COST-EFFECTIVE, SENSITIVE, AND SPECIFIC
ASSAYS FOR BONE TURNOVER MARKERS (BTMS) WOULD COMPLEMENT THE
MEASUREMENT OF BMD IN THE MANAGEMENT OF OSTEOPOROSIS
Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab.
2016 Nov-Dec;20(6):846-852. doi:

18. THE BTMS ARE GROUPED INTO TWO CATEGORIES BASED ON THE METABOLIC PHASE DURING WHICH THEY ARE
PRODUCED AS:
1. BONE FORMATION MARKERS :BY-PRODUCTS OF COLLAGEN SYNTHESIS: PROPEPTIDES OF TYPE 1
COLLAGEN: (C-TERMINAL: P1CP, N-TERMINAL: P1NP).OSTEOBLAST ENZYMES: ALKALINE
PHOSPHATASE (ALP) (TOTAL AND BONE-SPECIFIC) MATRIX PROTEINS: OSTEOCALCIN (OC).
2. BONE RESORPTION MARKERS.COLLAGEN DEGRADATION PRODUCTS: TELOPEPTIDES OF TYPE 1
COLLAGEN (C-TERMINAL: CTX-1 AND CTX-MATRIX METALLOPROTEINASES [MMP], N-TERMINAL: NTX-1)
HYDROXYPROLINE PYRIDINIUM CROSSLINKS (PYRIDINOLINE [PYD], DEOXYPYRIDINOLINE [DPD]),
NONCOLLAGENOUS PROTEINS: BONE SIALOPROTEIN, OSTEOCLASTIC ENZYMES: TARTRATE-RESISTANT
ACID PHOSPHATASE CATHEPSIN K, OSTEOCYTE ACTIVITY MARKERS: RECEPTOR ACTIVATOR OF
NUCLEAR FACTOR KAPPA-B LIGAND (RANKL) OSTEOPROTEGERIN (OPG) DICKKOPF-RELATED PROTEIN 1

19. PERIOSTEUM
DERIVED FROM THE GREEK WORD ‘PERI’ MEANING SURROUNDING AND ‘OSTEON’
MEANING BONE.
COVERS THE EXTERNAL BONE
EXCEPT FOR THE ARTICULAR CARTILAGE SURFACES, THE INSERTIONS OF
TENDONS, LIGAMENTS, JOINT CAPSULES, INTEROSSEOUS MEMBRANES
ALLOWS SOME LIGAMENTS, TENDONS, AND JOINT CAPSULES TO ATTACH TO BONE.
PROVIDES A SOURCE OF CELLS THAT CAN FORM NEW BONE OR CARTILAGE.

20. LAYERS :
AN OUTER FIBROUS: DENSE IRREGULAR CT
INNER CAMBIUM :
OSTEOBLASTS+OSTEOCLASTS
PERIOSTEUM IS ATTACHED TO THE BONE
THROUGH STRONG COLLAGENOUS FIBERS,
SHARPEY FIBRES
OUTER FIB DIVIDED INTO SUP+DEEP PORTION
S- GENERALLY INELASTIC, HIGHLY
VASCULARIZED, RICH NEURAL NETWORK
D- FIBROELASTIC, NOT HIGHLY
VASCULARIZED,PERIOSTEAL TENDON
ATTACHMENTS USUALLY TERMINATE HERE

21. INNER CAMBIUM LAYER
HIGHLY CELLULAR, COMPOSED OF MESENCHYMAL PROGENITOR CELLS,DIFFERENTIATED
OSTEOPROGENITOR CELLS, OSTEOBLASTS+FIBROBLASTS
AFTER A FRACTURE, PROGENITOR CELLS DEVELOP INTO OSTEOBLASTS &
CHONDROBLASTS WHICH ARE ESSENTIAL FOR HEALING
RESPONSIBLE FOR GIRTH
THICKEST IN FETUS, BECOMES PROGRESSIVELY THINNER WITH AGE
IN ADULTS, CANNOT BE DISTINGUISHED FROM OVERLYING FIBROUS LAYER

22. CHANGES IN PERIOSTEUM WITH AGE
● THE THICK CELLULAR VASCULAR PERIOSTEUM OF INFANTS AND CHILDREN READILY FORMS NEW
BONE.
● SHOWS THIS CAPACITY WHEN OSTEOMYELITIS OR TRAUMA DESTROYS THE DIAPHYSIS OF A
YOUNG INDIVIDUAL'S BONE,THE PERIOSTEUM REGENERATES A NEW DIAPHYSIS.
● WITH INCREASING AGE PERIOSTEUM BECOMES THINNER+LESS VASCULAR AND ABILITY TO FORM
NEW BONE DECREASES
● CELLS OF THE DEEPER LAYER BECOME FLATTENED AND QUIESCENT, ALTHOUGH THEY
CONTINUE TO FORM NEW BONE THAT INCREASES BONE DIAMETER

24. BLOOD SUPPLY OF BONE
RECEIVES 5-10% OF CARDIAC OUTPUT
3 SOURCES OF BLOOD SUPPLY:
● NUTRIENT ARTERY SYSTEM
● METAPHYSEAL AND EPIPHYSEAL SYSTEM
● PERIOSTEAL SYSTEM

25. NUTRIENT ARTERY SYSTEM
HIGH PRESSURE SYSTEM THAT BRANCHES FROM
MAJOR SYSTEMIC ARTERIES
ENTER THE CORTEX THROUGH THE NUTRIENT
FORAMEN
IN MEDULLARY CAVITY IT DIVIDES INTO ASCENDING
AND DESCENDING BRANCHES
SUPPLIES BONE MARROW AND INNER 2/3RD OF THE
DIAPHYSIS
FAMOUS MNEMONIC : “TO THE ELBOW I GO, FROM
THE KNEE I FLEE”

26. METAPHYSEAL SYSTEM
DERIVED FROM NEIGHBOURING
SYSTEMIC VESSELS.
ARISES FROM ANASTOMOSIS
AROUND THE JT
THESE ARTERIES ENTER THE
METAPHYSIS AT THE MARGIN OF
THE JT CAPSULE AND ANASTOMOSE
WITH SPIRAL BRANCH OF NUTRIENT
ARTERY

27. EPIPHYSEAL SYSTEM
IT HAS OPENINGS THAT PERMIT
PATHWAY FOR A LARGE NUMBER
OF VESSELS
SUPPLIES RESTING, GERMINAL,
PROLIFERATIVE, AND UPPER
HYPERTROPHIC LAYERS BY
DIFFUSION.

28. PERIOSTEAL SYSTEM
INTRINSIC PERIOSTEAL : FIBROUS LAYER OF PERIOSTEUM. (A) A SHORT VESSEL PATTERN,
WHERE THERE WERE MANY SMALL VESSELS WITH NO PREDOMINANT DIRECTION; (B) A
CIRCULAR PATTERN, WHERE THE VESSELS ENCIRCLED THE BONE; (C) A LONGITUDINAL
PATTERN, WHERE THE VESSELS RAN PARALLEL TO THE LONG AXIS OF THE BONE.
MUSCLOPERIOSTEAL: CONNECTIONS BETWEEN THE MUSCLE CIRCULATION AND THE
PERIOSTEAL VESSELS AT THE SITES OF MUSCLE ORIGIN
FASCIOPERIOSTEAL: CONSISTED OF BRANCHES FROM A LIMB ARTERY THAT RAN IN A FASCIAL
PLANE BETWEEN MUSCLES TO SUPPLY THE PERIOSTEUM
CORTICAL CAPILLARY ANASTOMOSIS: CAPILLARIES THAT RAN IN THE BONE CORTEX BETWEEN
THE INTRAMEDULLARY CIRCULATION AND THE PERIOSTEAL VESSELS

30. REFERENCES
Simpson AH. The blood supply of the periosteum. J Anat. 1985 Jun;140 ( Pt 4)(Pt 4):697-704.
Turek orthopedics and their principles
Shetty S, Kapoor N, Bondu JD, Thomas N, Paul TV. Bone turnover markers: Emerging tool in the management of
osteoporosis. Indian J Endocrinol Metab. 2016 Nov-Dec;20(6):846-852.

31. THANKYOU!