Bone Structure and Growth

Bone Structure

• Bone is a living tissue that provides support, protection, and movement for the body
• Compact bone, also known as cortical bone, is dense and stiff with low porosity (5-25%) making up the majority of human bone (~80%)
• Trabecular bone (also known as cancellous or spongy bone) is light and spongy with high porosity (up to 70%)
• Long bones have a diaphysis (shaft) made of compact bone, and epiphyses (ends) made of trabecular bone
• The epiphyseal growth plate is responsible for bone growth and fuses with the metaphysis around age 18, ending growth

Bone Growth

• Ossification is the process of bone formation, starting in cartilage during fetal development
• Bone growth occurs at the growth plate in childhood/adolescence through cartilage proliferation, controlled by growth hormone and insulin-like growth hormone (IGF-1)
• Once the growth plate fuses, cartilage proliferation and elongation cease, and bone is vascularized and ossified
• The osteon is the basic unit of bone growth, consisting of concentric circles of collagen deposition around a blood vessel, known as a Haversian canal
• Collagen is mineralized with hydroxyapatite (Ca10(PO4)6(OH)2) during ossification

Bone Cells

• Osteoblasts promote bone formation, laying down osteoid and initiating mineralization
• Osteoclasts promote bone reabsorption, removing mineralization and liberating calcium and phosphate
• Osteocytes originate from osteoblasts and facilitate the transfer of mineral from inside bone to growth surfaces
• Osteocytes have cytoplasmic projections that sense mechanical load on bone and communicate with osteoblasts

Bone Remodeling

• Bone turnover continues throughout life, remodeling the adult skeleton every 10 years with 1 million Bone Metabolic Units (BMUs) operating at any one time
• Bone remodeling balances mineralization through activation of osteoblasts and osteoclasts, enabling adaptation to mechanical loading, fracture healing, and preventing bone fatigue
• Osteocytes communicate mechanical strain to osteoblasts and PTH signaling, triggering a chain reaction leading to osteoclast activation
• Growth factors stimulate osteoblast formation, depositing new osteoid for mineralization, resulting in no net loss of bone over the 120-day bone remodeling cycle
• Bone remodeling involves four distinct phases: resorption, reversal, formation, and quiescence

Calcium Regulation

• Calcium is essential for many physiological processes including neurotransmitter release, muscle contraction, hormone and enzyme secretion
• Calcium exists in three forms in body fluids: ionized (free), protein-bound, and anion-bound (phosphate, citrate, and oxalate)
• Ionized calcium (Ca2+) mediates most physiological functions
• Acid-base status influences bound Ca2+ levels: acidosis increases free Ca2+ and alkalosis decreases free Ca2+ through protein binding

Parathyroid Hormone (PTH)

• PTH is the primary regulator of free Ca2+ in the body
• Released from the parathyroid glands by chief cells when plasma Ca2+ is low
• Detected by a membrane-bound G-protein coupled receptor, which regulates cAMP levels
• Decreases in Ca2+ increase cAMP and stimulate PTH release, while increases in Ca2+ inhibit PTH release

Vitamin D

• The active form of vitamin D is 1,25 dihydroxycholecalciferol (DHCC), also known as calcitriol
• Synthesized from precursor vitamin D3 (cholecalciferol) through two hydroxylation steps
• 25-hydroxylation occurs in the liver, catalyzed by 25-hydroxylase
• 1α-hydroxylation in the kidney, catalyzed by 1α-hydroxylase, is the rate-limiting step and a crucial regulatory site
• Vitamin D acts on intracellular receptors as a steroid-like structure

Vitamin D Action

• Vitamin D promotes Ca2+ absorption in the duodenum through Ca2+ channels and binding proteins (calbindin)
• It also stimulates the synthesis of components involved in Ca2+ and phosphate absorption in the gut
• In the kidney tubules, vitamin D promotes Ca2+ and PO43- reabsorption
• Overall effect of vitamin D is to increase the flux of Ca2+ and phosphate into bone

Osteoporosis

• A systemic skeletal disease characterized by low bone mass and weakened bone microarchitecture, leading to increased fracture risk
• Affects 33% of women after age 50 and 20% of men after age 50
• Increases in the aging population escalate the risk
• Hip fractures are more common in women than breast cancer

Vitamin D Deficiency

• Rickets in children, characterized by abnormal amounts of unmineralized osteoid causing bowing of long bones
• Osteomalacia in adults, characterized by bone weakness due to unmineralized osteoid, without bowing