Bones II (Fall 2024) PDF

Bones & Skeletal Tissue II  What looks Bone Development odd about these deposits? Ossification (osteogenesis) is the process of b...

Bones & Skeletal Tissue II  What looks Bone Development odd about these deposits? Ossification (osteogenesis) is the process of bone tissue formation by osteoblasts This is a distinct process from that of calcification Formation of bony skeleton begins ~ 6 weeks after fertilization of embryo Postnatal bone growth occurs until early adulthood Bone remodeling and repair are lifelong Formation of the Bony Skeleton Up to about week 8 of life, skeleton consists of fibrous membranes and hyaline cartilage Ultimately replaced with bone tissue Endochondral ossification Process of bone development from (by replacing) hyaline cartilage Requires breakdown of hyaline cartilage Begins at primary ossification center in center of shaft Form most of skeleton, except flat bones of skull, mandible and clavicles Intramembranous ossification Process of bone development from fibrous membrane Formation of skull, mandible and clavicles Review Slide Intramembranous Ossification Begins within fibrous connective tissue membranes Forms flat bones of skull, mandible and clavicle Stem cells differentiate into osteoblasts which secrete and deposit calcium Connective tissue of the matrix differentiate into red bone marrow  Long bones grow lengthwise by interstitial (longitudinal) growth of epiphyseal plate Bones increase thickness through Postnatal appositional growth Bone Growth A balance between building bone and breaking down bone = allows for thickening without becoming too heavy Bones growth continues through adolescence Some facial bones continue to grow slowly through life Growth in Length of Long Bones Interstitial growth requires presence of epiphyseal cartilage in the epiphyseal plate Epiphyseal plate maintains constant thickness Rate of cartilage growth on one side balanced by bone replacement on other Chondrocytes on the epiphyseal side of the plate divide: one cell remains undifferentiated near the epiphysis, and one moves toward shaft of bone to eventually mature and calcify….essentially becoming bone (results in bone lengthening) Growth in Length of Long Bones Near end of adolescence, chondroblasts divide less often Epiphyseal plate thins, then is replaced by bone Epiphyseal plate closure occurs when epiphysis and diaphysis fuse Bone lengthening ceases Females: occurs around 18 years of age Males: occurs around 21 years of age  Growing bones widen as they lengthen through appositional growth Can occur throughout life Bones thicken in response to increased Growth in stress from muscle activity or added weight Osteoblasts beneath periosteum secrete Width bone matrix on external bone (Thickness) Osteoclasts remove bone on endosteal surface Usually more building up than breaking down which leads to thicker, stronger bone that is not too heavy  Growth hormone: most important hormone in stimulating epiphyseal plate activity in infancy and childhood Thyroid hormone: modulates activity of growth hormone, ensuring proper Hormonal proportions Regulation of Testosterone (males) and estrogens (females) at puberty: low levels promote Bone Growth adolescent growth spurts High levels end growth by inducing epiphyseal plate closure Excesses or deficits of any hormones cause abnormal skeletal growth Bone Remodeling About 5–7% of bone mass is recycled each week Spongy bone replaced ~ every 3-4 years Compact bone replaced ~ every 10 years Bone remodeling consists of both bone deposit and bone resorption Occurs at surfaces of both periosteum and endosteum Remodeling units: packets of adjacent osteoblasts and osteoclasts coordinate remodeling process Review: Bone Resorption Resorption is function of osteoclasts Secrete lysosomal enzymes and protons (H+) that digest matrix Osteoclasts also phagocytize demineralized matrix and dead osteocytes Once resorption is complete, osteoclasts undergo apoptosis Osteoclast activation involves PTH (parathyroid hormone) and immune T cell proteins Review: Bone Deposit New bone matrix is deposited by osteoblasts Trigger for deposit not confirmed but may include: Mechanical signals Increased concentrations of calcium and phosphate ions for hydroxyapatite formation Matrix proteins that bind and concentrate calcium Appropriate amount of enzyme alkaline phosphatase for mineralization Control of Remodeling Remodeling occurs continuously but is regulated by genetic factors and two control loops Hormonal controls Negative feedback loop that controls blood Ca2+ levels Calcium functions in many processes, such as nerve transmission, muscle contraction, blood coagulation, gland and nerve secretions, as well as cell division 99% of calcium are found in bone Intestinal absorption of Ca2+ requires vitamin D Response to mechanical stress Hormonal Control Parathyroid hormone (PTH): produced by parathyroid glands in response to low blood calcium levels Stimulates osteoclasts to resorb bone Calcium is released into blood, raising levels PTH secretion stops when homeostatic calcium levels are reached Calcitonin: produced by thyroid gland in response to high levels of blood calcium levels Effects are negligible, but at high pharmacological doses it can lower blood calcium levels temporarily Control of Remodeling: Response to Mechanical Stress Bones reflect stresses they encounter Bones are stressed when weight bears on them or muscles pull on them Wolf’s law states that bones grow or remodel in response to demands placed on them Stress is usually off center, so bones tend to bend Bending compresses one side, stretches other side Diaphysis is thickest where bending stresses are greatest Bone can be hollow because compression and tension cancel each other out in center of bone Wolf’s law also explains: Handedness (right- or left-handed) results in thicker and stronger bone of the corresponding upper limb Curved bones are thickest where most likely to buckle Trabeculae form trusses along lines of stress Large, bony projections occur where heavy, active muscles attach Weightlifters have enormous thickenings at muscle attachment sites of most used muscles Bones of fetus and bedridden people are featureless because of lack of stress on bones Clinical Relevance Bone Fractures are breaks in the Bone During youth, most fractures result from trauma, in old age, most result from weakness of bone due to bone thinning 3 “either/or” fracture classifications Position of bone ends after fracture Nondisplaced: ends retain normal position Displaced: ends are out of normal alignment Completeness of break Complete: broken all the way through Incomplete: not broken all the way through Whether skin is penetrated Open (compound): skin is penetrated Closed (simple): skin is not penetrated Fracture Treatment and Repair Treatment involves reduction, the realignment of broken bone ends Closed reduction: physician manipulates to correct position Open reduction: surgical pins or wires secure ends Immobilization of bone by cast or traction is needed for healing Time needed for repair depends on break severity, bone broken, and age of patient Fracture Treatment and Repair Repair involves four major stages: 1. Hematoma formation 2. Fibrocartilaginous callus formation 3. Bony callus formation 4. Bone remodeling Fracture Treatment and Repair 1. Hematoma formation Torn blood vessels hemorrhage, forming mass of clotted blood called a hematoma Site is swollen, painful, and inflamed Fracture Treatment and Repair 2. Fibrocartilaginous callus formation Capillaries grow into hematoma Phagocytic cells clear debris Fibroblasts secrete collagen fibers to span break and connect broken ends Fibroblasts, cartilage, and osteogenic cells begin reconstruction of bone Create cartilage matrix of repair tissue Osteoblasts form spongy bone within matrix This mass of repair tissue is called fibrocartilaginous callus Fracture Treatment and Repair 3. Bony callus formation Within one-week, new trabeculae appear in fibrocartilaginous callus Callus is converted to bony (hard) callus of spongy bone Bony callus formation continues for about 2 months until firm union forms Fracture Treatment and Repair 4. Bone remodeling Begins during bony callus formation and continues for several months Excess material on diaphysis exterior and within medullary cavity is removed Compact bone is laid down to reconstruct shaft walls Final structure resembles original structure Responds to same mechanical stressors  Imbalances between bone deposit and bone resorption underlie nearly every disease that affects Bone the human skeleton. Disorders Three major bone diseases: Osteomalacia and rickets Osteoporosis Paget’s disease Osteomalacia and Rickets Osteomalacia Bones are poorly mineralized Osteoid is produced, but calcium salts not adequately deposited Results in soft, weak bones Pain upon bearing weight Rickets (osteomalacia of children) Results in bowed legs and other bone deformities because bones ends are enlarged and abnormally long Cause: vitamin D deficiency or insufficient dietary calcium Osteoporosis Osteoporosis is a group of diseases in which bone resorption exceeds deposit Matrix remains normal, but bone mass declines Spongy bone of spine and neck of femur most susceptible Vertebral and hip fractures common Osteoporosis Risk Factors Most often aged, postmenopausal women Affects 30% of women aged 60–70 years and 70% by age 80 Estrogen plays a role in bone density, so when levels drop at menopause, women run higher risk Men are less prone due to protection by the effects of testosterone Additional risk factors for osteoporosis: Insufficient exercise to stress bones Diet poor in calcium and protein Smoking Genetics Hormone-related conditions Hyperthyroidism Diabetes mellitus Consumption of alcohol or certain medications Paget’s Disease Excessive and haphazard bone deposit and resorption cause bone to grow fast and develop poorly Called Pagetic bone Very high ratio of spongy to compact bone and reduced mineralization Usually occurs in spine, pelvis, femur, and skull Rarely occurs before age 40 Cause unknown: possibly viral Treatment includes calcitonin and Moth-eaten appearance of bisphosphonates bone with Paget’s disease Developmental Aspects of Bone Embryonic skeleton ossifies predictably, so fetal age is easily determined from X rays or sonograms Most long bones begin ossifying by 8 weeks, with primary ossification centers developed by week 12 Birth to Young Adulthood At birth, most long bones ossified, except at epiphyses Epiphyseal plates persist through childhood and adolescence At ~ age 25, all bones are completely ossified, and skeletal growth ceases Fetal primary ossification centers at 12 weeks  In children and adolescents, bone formation exceeds resorption Males tend to have greater mass than females In young adults, both are balanced In adults, bone resorption exceeds formation Age-Related Bone density changes over lifetime are largely determined by genetics Changes in Gene for vitamin D’s cellular docking determines mass early in life and Bone osteoporosis risk at old age Bone mass, mineralization, and healing ability decrease with age beginning in fourth decade Except bones of skull Bone loss is greater in whites and in females