Bone Fractures and Bone Cells

• Osteocytes are bone cells.
• Bone deposition is the normal process of bone formation.
• Bone resorption is the normal process of bone breakdown, contributing to serum calcium in the bloodstream.
• Osteoblasts are specialized cells that participate in bone formation, known as deposition.
• Osteoclasts are specialized cells involved in bone breakdown, called resorption.

Fractures

• A fracture defined as a break in the continuity of a bone.
• Fractures occur when the applied force exceeds the tensile or compressive strength of the bone.
• Fracture incidence depends on the bone that is involved, age, and gender.
• The highest fracture incidence is seen in young males aged 15 to 24, followed by adults 65 years and older (females or males).
• Hip and wrist fractures are more common in females.
• An estimated 158 million hip fractures occurred worldwide in 2015.
• Falls, car accidents, and athletic injuries commonly cause fractures.
• Complete fractures are when the bone is broken all the way through.
• Incomplete fractures are when the bone is damaged, but still in one piece.
• Closed or simple fractures occur when the skin remains intact.
• Open or compound fractures are when the skin is broken.
• Comminuted fractures are when the bone breaks into more than two fragments.
• Linear fractures are defined when the fracture runs parallel to the long axis of the bone.
• Oblique fractures are when the shaft of the bone is slanted.

Pediatric Population Risk Factors

• Pediatric populations have a lower bone mineral content and low bone mineral density (BMD).
• Genetic factors and poor nutrition influence risk factors.
• Inadequate dietary calcium intake, milk avoidance, excessive carbonated beverage consumption, and lower vitamin D exposure increase the risk.
• A lack of weight-bearing physical activity impairs bone growth.
• Obesity is a contributing risk factor.
• Playing sports increases the risk of trauma and increases risk for fractures.

Older Adult Risk Factors

• Increasing age and general wear and tear on the body increase risk factors.
• Gender plays a role.
• Osteoporosis (fragility fracture), is especially seen in females with lower estrogen.
• Lifestyle choices such as smoking and alcohol increase risk factors.
• The use of steroids increases the risk.
• Having diabetes increases the risk.
• Previous fractures increase the likelihood of future fractures over the age of 65.

Pathophysiology of Fractures

• Bone breakage disrupts the periosteum and blood vessels in the cortex, marrow, and surrounding soft tissues.
• Bleeding occurs from the damaged bone ends and nearby soft tissue.
• A hematoma forms within the medullary canal, between the fractured bone ends, and beneath the periosteum.
• Bone tissue immediately adjacent to the fracture dies.
• Necrotic tissue and debris in the fracture area stimulate an intense inflammatory response.
• This response is characterized by vasodilation, plasma exudation, leukocyte infiltration and inflammatory leukocytes and mast cells.
• Cytokines, including transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and prostaglandins, are released.
• Cytokines and prostaglandins released encourage and promote healing.
• Within 48 hours after injury, vascular tissue invades the fracture area from surrounding soft tissue and marrow cavity and results in increased blood flow to the entire bone.
• Osteoblasts and osteoclasts become activated in the periosteum, endosteum, and marrow.
• Subperiosteal procallus (new bone) produces along the outer surface of the shaft and over the broken ends of the bone.
• Bone is unique, and after a fracture occurs, it can heal with normal tissue, not scar tissue.
• Healing occurs in three overlapping phases: the inflammatory phase, the repair phase, and the remodeling phase.
• The inflammatory phase lasts for 3–4 days, and bone tissue destruction triggers an inflammatory response and hematoma formation.
• The repair phase lasts several days and involves capillary ingrowth, mononuclear cells, fibroblasts which transform the hematoma into granulation tissue and osteoblasts within the procallus.
• The remodeling phase lasts months to years and involves unnecessary callus resorption and the forming of trabeculae.

Manifestations of Fractures

• Manifestations vary depending on the type and site of the fracture and soft tissue injury.
• Manifestations can include impaired function, unnatural alignment, swelling, and muscle spasms.
• Tenderness occurs and impaired sensation if nerves are damaged during the break.
• It can also manifest as usually trauma-related pain, which is often immediate and severe at the injury site.
• Subsequent pain is produced by muscle spasms, overriding of fracture segments, and damage to adjacent soft tissues.

Complications of Fractures

• Improper reduction and immobilization of fractured bone may result in nonunion, delayed union, or malunion.
• Nonunion is defined as a failure of bone ends to grow together.
• Delayed union is defined as union that will not occur until approximately 8 to 9 months after fracture.
• Malunion is defined as the healing of bone in a non-anatomic position.
• Broken bones can damage surrounding tissue, periosteum, and blood vessels in the cortex and marrow.
• Problems with joints, such as dislocation and subluxation, are most common in persons under 20 and are usually associated with fractures.
• In pediatric age groups, impacted growth plates can be impacted during fractures.
• If growth plates are impacted during fractures, it can result in shorter or crooked limbs.
• Older adults have a potentially increased mortality, pain, disability, depression and loss of independence.
• Older adults are at high risk of morbidity and mortality after osteoporotic fracture.

Evaluation and Diagnostics and Treatments of Fractures

• Evaluation and diagnostics for fractures includes X-ray studies.
• Treatments include closed manipulation, traction skeletal or skin traction, internal or external fixation.
• Splints, casts help with immobilization.
• Treatment of delayed union and nonunion fractures include the use of various methods designed to stimulate new bone formation.

Osteoporosis

• Simply stated, more bone resorption outpaces bone deposition, which is more bone loss than creation.
• Clients with osteoporosis develop weak bones.
• Classified as the most common disease affecting bone, affecting about 1.4 million Canadians.
• Complex, multifactorial chronic disease often progresses silently for decades until fractures transpire.
• Low bone mineral density (BMD), impaired structural integrity of bone, decreased bone strength, and increased risk of fracture.
• Those with the lowest BMD are most at risk of fracture.
• Old bone is reabsorbed faster than new bone is made.
• Bones lose density and become thinner and more porous.
• May continue until the skeleton is no longer strong.
• Bones fracture spontaneously or from falls that would not previously have caused fracture.
• Around age 30, bone resorption slowly exceeds bone formation.
• Osteoporosis is most common in females, a rate of one in two.
• Bone loss begins before menopause but becomes most rapid once the menopause starts.
• It persists throughout postmenopausal years.
• An estimated one in four men experiences osteoporosis-related fractures.
• Adults over age 50 with osteoporosis, prevalence is in the spine or femoral neck.
• Roughly 3% to 10% of men, and 7% to 35% of women have osteoporosis in the spine or femoral neck.
• Post-menopause is a risk factor due to decreased estrogen (which balances osteoclast/blast activity)
• A family history of osteoporosis and age over 60, Caucasian or Asian descent, and testosterone deficiency increase risk factors.
• Inadequate intake of vitamin D or calcium, tobacco use, high alcohol or caffeine consumption, physical inactivity, and drugs that lower serum calcium levels are increase risk.
• Anorexia nervosa (malnutrition) is also a risk factor.

Etiology of Osteoporosis

• Can be primary or idiopathic (most common): due to age-associated aging and calcium deficiency.
• Postmenopausal estrogen deficiencies lead to decreased bone density
• Secondary osteoporosis can occur from endocrine diseases.
• Hormone imbalances, diabetes, hyperparathyroidism and the adverse effects of drugs used long-term are increase risk.
• Drugs such as heparin, corticosteroids - glucocorticoids, phenytoin, barbiturates, and lithium also increase risk,.
• Tobacco and alcohol use increase risk factors.
• In healthy individuals, calcium comes from intestines.
• Osteoporosis develops when remodeling cycle - the process of bone resorption and bone formation is disrupted.
• With osteoporosis, there is no deposition happening.
• Bone demineralization leads to porous bones with decreased bone density,.

Role of Oxidative Stress in Osteoporosis

• When excess ROS accumulates.
• Oxidative stress leads to a loss of bone mass and bone strength.

Osteoclast Differentiation Pathway

• This pathway of osteoclast creation is disturbed..
• Directed by a series of processes, including proliferation, differentiation, fusion, and activation.
• Processes are controlled by hormones, cytokines, and paracrine stromal cell microenvironment.

OPG/RANKL/RANK System

• IL-1, IL-4, IL-6, IL-7, IL-11, IL-17, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), prostaglandin E2, and hormones interact to control osteoclasts.
• Normal bone homeostasis depends on the delicate balance between the cytokine receptor activator of RANKL, its receptor RANK, and its decoy receptor osteoprotegerin (OPG) so that normal deposition can occur.
• RANKL is a cytokine that activates the receptor RANK, expressed on osteoclasts and their precursors.
• RANKL suppresses apoptosis and prolongs osteoclast survival, thus promoting increased life span.
• OPG is a glycoprotein acting as an antagonist for RANKL to maintain homeostasis.
• OPG prevents RANKL from binding to and activating the RANK receptor on osteoclasts and their precursors,.
• Estrogen stimulates OPG secretion and down-regulates RANKL.
• RANKL expression to promote osteoclast formation is increased when estrogen levels decrease, such as in menopause.
• Glucocorticoids increase RANKL expression and inhibit OPG production by osteoblasts.
• Alterations can lead to osteoporosis
• The Skeletal system promotes osteoclast differentiation and activation as well as cytoskeletal reorganization and survival increase bone resorption and loss.
• The immune system enhances bone loss occurring in inflammatory bone diseases.
• The Vascular system has a physiologic significance of the OPG/RANKL/RANK system.
• The vascular system is in endothelial and smooth muscle cells.
• Depend on bone fractured.

Manifestations of Osteoporosis

• The main fractures are those of the trochanter of spongy bone becoming thin and sparse.
• Compact bone becomes porous, and fractures of femur, humerus, distal radius, ribs, vertebrae are most common.
• Most serious are hip fractures and pain with fragility fracture.
• Bones lose volume, become brittle and weak, and may collapse or become misshapen.
• Bone itself is innervated but muscles and tendons will also be affected by inflammation and infection.
• Manifestations include vertebral collapse, causing kyphosis, reduced pulmonary function as vertebrae/spine start to curve, and diminished height (in females).

Complications of Osteoporosis

• Fatal complications of osteoporotic fractures can include fat or pulmonary embolism that will jump into bloodstream and hemorrhage.
• Severe bleeding from fractures impact comorbidities’ abilities.
• 20% of people with hip fracture die from surgical complications such as infection, hemorrhage, or spesis.

Evaluation and Diagnostics

• Osteoporosis is asymptomatic unless a fracture has occurred, and diagnosis can be delayed.
• By the time abnormalities are detected by X-ray, 25% to 30% of bone may be gone.
• Dual X-ray absorptiometry (DXA) estimates bone density, but does not provide information about bone strength or fracture risk.
• Bone strength can estimated with an online tool called Fracture Risk Assessment (FRAX), which that predicts 10-year probability of fracture.
• Other evaluation procedures include computed tomography scans, where serum calcium, phosphorus, alkaline phosphatase, and protein electrophoresis are measured.
• Body calcium levels are also measured by neuron activation analysis and calcium-49 with wholecounter.
• Prevention of osteoporosis is vital, as it is difficult to treat or reverse and can have a lot of potential complications.
• Most treatment focuses on preventing fractures to maintain function.
• Regular moderate weightbearing exercises and diet is important.
• Intake of calcium to maintain normal calcium balance, especially throughout adolescence.
• Adequate magnesium and potential drug: bisphosphonates and estrogen replacement therapy to control OPG/RANK expression balance.
• The role of calcium in preventing and treating osteoporosis is controversial.
• Diets that are higher in fruit and vegetable contribute to higher BMD.
• Vitamin K2, docosahexaenoic acid or DHA are found in purified fish oil, that has a positive impact on bone health.
• Magnesium is also important; required for normal calcium absorption to prevent brittle bones.

Dietary Recommendations

• Increase intake of Omega-3 fatty acids which include oily fish twice per week.
• Get a safe level of sun exposure.
• Eat rich vitamin D dietary sources or take vitamin D supplements.
• Increase Vitamin K in leafy vegetables.

Osteoarthritis

• Defined as a degenerative, age-onset joint disease.
• Characterized by the breakdown over time (wear and tear) of joints and cartilage changes in bone or tissue ligaments and muscle.
• It is considered an age-related disorder of articular or synovial joints, which includes weight-bearing joints.
• The most common causes of disability are in the knees, spine, hips, and hands.
• A second most common cause of disability in Canada.
• 43 million individuals are impacted by this disease.
• Changes lead to joint dysfunction, pain, stiffness, functional limitations and loss of walking.

Risk Factors for Osteoarthritis

• Increased age is the biggest risk factor for developing this disease.
• Can effect individuals of 45 and under.
• Sex plays a role with it more common in females.
• Certain medications include colchicine.
• Indomethacin stimulates collagen degrading enzymes.
• Steroid use is also a risk.
• Abnormal knee alignment, varus or valgus, creates pressure imbalance, which also increases risk.

Etiology of Osteoarthritis:

• This type of arthritis can be primary or idiopathic.
• The exact cause is unknown, but is associated with increasing age while individuals ages at the same age.
• It is commonly diagnosed with a preceding trauma.
• Risk factors may include: age, obesity, wear and tear of joints, genetics and genetics trauma.
• Can be of 2nd degrees.
• Pre-existing joint abnormality: congenital joint disorder.
• Mechanical stress joint, neurological disorders, certain pharmaceutical, high joint immobility, obesity, estrogen levels, hormones levels.

Is OA a Noninflammatory Joint Disease?

• This type of arthritis is classified as no inflammatory because the key issue is not inflammatory.
• There are various cytokines that have been linked with arthritis.
• Low grade effects.
• Process of cartilaginous issues that leads to x-ray, MRIs.

Pathophysiology

• The Primary defeat in OA is joint damaged that results in loss in cartilage and bone, biochemical issues and is also related issues.
• There also is inflammation and ECM.
• Controcytes and proteins are both destroyed in the cycle, resulting in high amount of degregation.

Surface

• This leads to the breakdown of surface layers of cartilage which makes it thinner and less bone to cause sclerotic.
• This creates an effect to damage joints.
• There is an issue of fluid with joints.
• This lead to initiation and destabilized bones.

Manifestations of Osteoarthritis

• Deep aching and tenderness.
• Is is commonly painful while waking in affected legs.
• Resting can help pain.
• The start has gradual effect and will be visible over time.
• Joint stiffness and creaking.
• Enlarged effect.
• Unsteady presentation.
• Restricted motor effect.
• Effect on ligaments.
• The major effects would be from: pain, damage and restricted joint movement
• Damage includes: muscle pain, strain and tendon insertion.
• The hands of those with OA has unique deformation called Bouchard Nodes Individual
• (subjective prort is important, eg. pain.)
• Look at the patient to exam the joint to see is there damage. There are many tests to run.
• CT & X-RAY & MRI's.

Treatment:

• Resting Joint until inflimation fades for some while before a PT may recommend a low-impact workout.
• Canes, Bracerss.
• Medication to help ease pain.
• Possible surgery for the patient but is no longer needed to help with workouts.
• Increase intake of fatty acids and sun exposure and foods rich in vitamins.

Medical Management

• Medical pharmacotheray, such as: Non-opioid (such as Acetaminophen)
• Selective and Non-Selective Cox-2 for pain and inflammations (such as ibuprofen) to also use proton pump inhibitors.
• Alendronate for biophospahte related issues.
• Pain can be immediate and may reduce the pain to let patients continue the daily activities.
• There is a need to check the underlying cause of joint inflammatory.
• Cox inhibitoon has 2 types: there is cyclooxygenase and Lipoxygenase that reduces the rate of prostaglandin effects.
• NSID can help relive from sever pains.
• Biphosphonates helps to improve the amount of osteoclast to improve bone support.