Bone remodeling and fracture repair

Injury triggers inflammation first: local vessels widen and become leaky, fluid and white blood cells enter, and macrophages begin clearing debris. Repair follows.

• Scar tissue replaces the damaged cells:
• Correct: Inflammation: vessels widen and leak, and the area swells:
• Stem cells rebuild the tissue immediately:

Osteoclasts, huge fused cells of the macrophage line, pump out hydrogen ions and release lysosomal enzymes onto the bone.

• Correct: Osteoclast:
• Osteoblast:
• Osteogenic cell:

Blood that escapes from a torn vessel clots. In a fracture, the clot around the break is the fracture hematoma, the first stage of repair.

• A callus:
• Correct: A blood clot:
• An abscess:

The female curve drops steeply between about 50 and 60, far faster than at any other time or in men. Those are the years around the end of a woman's reproductive life, when a hormonal brake on osteoclasts is lost.

• Correct: Women, from about 50 to 60: Correct. The steepest drop on the graph is the female curve in the fifties.
• Men, from about 30 to 40: Men are at or near their peak at 30 to 40; their curve is almost flat there.
• Men, from about 80 to 100: Men do lose bone steadily late in life, but the slope is gentle compared with women in their fifties.
• Women, from about 70 to 100: After 60, the female curve falls again at a gentle, steady rate, much like the male curve.

Repair runs from hematoma to soft callus to bony callus to remodeling. The hematoma is invaded by vessels and becomes a soft callus of collagen and cartilage; that cartilage is replaced by spongy bone, as in endochondral ossification; and remodeling restores compact bone and the bone's shape over months to years.

• Correct order: 1. Blood from torn vessels clots around the break, forming a fracture hematoma 2. Capillaries grow in and fibroblasts and chondrocytes build a fibrocartilaginous callus 3. Osteoblasts replace the cartilage with spongy bone, forming a bony callus 4. Osteoclasts remove extra bone and compact bone replaces the spongy bone of the shaft

Bone follows load. Without load, osteocytes shift their signals toward resorption: osteoclasts work harder, osteoblasts less, bone mass falls and calcium is released. Spongy bone, with its large surface, loses bone fastest.

• Load on the leg bones: down. Lying in bed, the legs no longer carry body weight or the pull of walking muscles.
• Osteoclast activity: up. Unloaded osteocytes release more of the signal that makes osteoclasts form, so resorption rises.
• Osteoblast activity: down. Unloaded osteocytes release more of the signal that holds osteoblasts back, so formation falls.
• Bone mass: down. With resorption above formation, each remodeling cycle removes more bone than it replaces: Wolff's law in reverse.
• Calcium released from the leg bones: up. Osteoclasts dissolve mineral, so more calcium leaves the bones; much of it is lost in the urine.

Wolff's law: bone adapts to the loads placed on it. Years of hitting loaded the racket arm's bones heavily, osteocytes signaled for more formation and less resorption, and bone was added until the thicker wall brought strain back down.

• Her racket arm received more calcium from the blood: Both arms receive the same blood, so a difference between them cannot come from something carried in it.
• Her racket arm's growth plates closed later: Growth plates in the two arms close at about the same time, and thicker walls reflect width, not length.
• Correct: Repeated heavy loading made the bone add mass: Correct. Load drives bone formation.
• Her racket arm has more red marrow: Marrow type does not thicken the bone's wall, and adult upper arm shafts hold mainly yellow marrow.

A child's bone has proportionally more collagen and less mineral than an adult's, so it is more flexible. Under a bending load it can crack on the stretched side and bend on the other, like a green twig.

• Children's bones have no compact bone: Children's bones have compact bone walls, just thinner than adults'.
• Correct: Children's bones hold more collagen relative to mineral: Correct. More flexible bone bends and breaks partway.
• Children's bones have open growth plates in the shaft: Growth plates are near the ends of the bone, not in the shaft where greenstick fractures occur.
• Children have fewer osteoclasts: Osteoclast numbers do not explain how a bone breaks in the moment of injury.

In osteoporosis, resorption has outpaced formation for years, so there is too little bone, with thin and disconnected trabeculae and a thinner compact wall. The bone that remains has normal mineral in its matrix.

• The bone present is soft because it lacks mineral: Soft, poorly mineralized bone is a different disease, caused by too little vitamin D. In osteoporosis the mineral content of the remaining bone is normal.
• The bone is dense but brittle from faulty collagen: Faulty collagen causes brittle bone disease from childhood, not the age-related loss of bone mass in osteoporosis.
• Correct: There is too little bone, but what remains is normally mineralized: Correct. Osteoporosis is a lack of bone, not a lack of mineral in the bone.
• The trabeculae are thicker to make up for weakness: Trabeculae thin and disconnect in osteoporosis; they do not thicken.

Early healing depends on capillaries growing into the hematoma and a soft callus bridging the gap. Too much movement tears these fragile structures again and again, so the bony callus is delayed and the break may fail to join.

• Faster healing of the break from the added load on it: Load helps bone once the callus is firm, during remodeling. Early movement at the break itself disrupts the soft callus.
• Correct: Delayed union from repeated disruption of the callus: Correct. Motion keeps breaking the new vessels and callus.
• A larger fracture hematoma that heals stronger: More bleeding does not produce a stronger repair; it only adds swelling.
• Earlier conversion of spongy bone to compact bone: Remodeling to compact bone comes last and needs a stable bony callus first.