Bone Flashcards
What are the functions of the main types of bone cells?
Osteogenic cells: Develop into osteoblasts
Osteoblasts: bone formation (build)
Osteoclasts: Bone resorption
Osteocytes: maintain mineral concentration of the matrix
What are osteons?
They are a subunit of bone structure. Osteons are composed of concentric rings of osteocytes with their dark nuclei in lacunae and this processes called canaliculi
Each osteon has a central Haversian canal with the vascular supply that reaches osteocytes via the canaliculi
What mineral primarily composes the bones?
Hydroxyapatite crystal
Serum calcium, Vitamin D, and PTH levels control the metabolism of bone
What is the definining characteristic of trabecular bone?
This part of the bone is spongy and it serves an absorbent of stresses put on the bone. They also provide rigidity without conferring a lot of weight
The pores in trabelular bone contain either yellow or red marrow
What is osteoporosis?
Multi factorial disease characterized by absolute reduction of the total bone mass. Bone density is significantly reduced. The bones are the same size, but contain less mineral material, effectively reducing bone density and strength
What is the incidence of osteoporosis?
1.4 Million Canadians are affected, mainly postmenopausal women and the elderly
Affects 1/4 of women over 50, but only 1/8 of men over 50
70-90% of hip fractures are caused by osteoporosis
What are the clinical criteria for osteoporosis diagnosis?
Reduction in bone mineral density by 2.5 STDEVs at the lumbar spine, femur neck, or total hop
What is the clinical criteria for osteopenia diagnosis?
This is a less severe version of osteoporosis
Reduction of bone mineral density between 1 and 2.5 STDEVs
What are the risk factors for primary osteoporosis?
Unknown etiology, but certain factors predispose patients to osteoporosis:
Age-related changes in metabolism (primary cause)
Low initial bone mass (small frame)
Ethnicity (affects White and Asian more than Black people)
Bad dietary habits (smoking, low Ca2+ and Vitamin D)
Hormones (menopause=low estrogen)
What is the difference between primary and secondary osteoporosis?
In primary osteoporosis, the etiology is unknown, but it is the most common form
In secondary osteoporosis, it is usually related to another disease (autoimmune, inflammatory, or nutrient deficiencies)
What are some diseases that may cause secondary osteoporosis?
Essentially any disease that can reduce activity and load on bones = decreased bone mass = increased osteoporosis risk
Autoimmune Disorders (inflammatory factors affect bone turnover):
Rheumatoid Arthritis
Lupus
Multiple Sclerosis
Ankylosing spondylitis
GI Disorders (absorption of nutrients is decreased):
Celiac disease
IBD
Weight loss surgery
Medical procedures:
Gastrectomy
GI bypass
Cancer (invasion of bone):
Breast cancer
Prostate Cancer
Hematologic/Blood disorders:
Leukemia
Multiple myeloma
Sickle cell disease
Neurological Disorders (limits mobility and weight bearing activities):
Stroke
Parkinson’s disease
MS
Spinal injuries
Mental health (poor nutrition and activity):
Depression
Eating disorders
Endocrine function (hormonal effects):
Diabetes
Hyperparathyroidism
Hyperthyroidism
Cushing’s syndrome
Premature menopause
What is female athlete triad?
This is a situation where a young woman does excessive exercise, whilst not maintaining nutrition. She also has looses nutrients during menstruation
This can greatly increase her risk of developing osteoporosis in the future
What is the pathogenesis of osteoporosis?
Osteoporosis is caused by more more cells being resorted than being deposited
This imbalance causes a progressive loss of bone density and thinning
Review slide 17 for a detailed look at the regulation of bone remodelling and what can go wrong to cause osteoporosis
What is the relevance of RANKL in osteoporosis?
RANKL is a ligand produced by osteoblasts, it production is unregulated when estrogen levels decline. When RANKL binds to osteoclasts, it stimulates their activity an inhibits osteoblast activity
In postmenopausal women, estrogen levels decline, which up-regulates the production of RANKL. More RANKL binding to osteoclasts causes (bone resorption) to go into overdrive.
What are some consequences of osteoporosis?
Hip(falling, normal movement) and vertebral (kyphosis) fractures
Radial fractures (break while catching yourself fall)
Loss of height and stooped posture (successive vertebral fractures)
What treatments are available for osteoporosis?
BIsphosphonates
Denosumab
Hormone Therapy
SERM (selective estrogen receptor modulators)
What is the mechanism of action for bisphosphonates?
Slow down the bone resorption action of the osteoclasts and promote osteoclast apoptosis.
These drugs need to be taken and stay in an upright position. If patient lies down, it can cause esophageal pain
Ex. Alendronate, etidronate, risedronate
Why is it a bad idea to be on bisphosphonates for an extended period of time without breaks (10 years straight)?
No bone remodelling due to inhibited osteoclasts can increase fracture risk (opposite effect of bisphosphonates)
What is the mechanism of action for Denosumab?
A monoclonal antibody that binds to RANKL. Once binded to RANKL, it prevents RANKL from promoting osteoclast activity
Effective and useful for patients that cannot tolerate bisphosphonates, but it is more expensive
What is the mechanism of hormone therapy in osteoporosis?
Increased estrogen down regulates the production of RANKL by osteoblasts. Due to this inhibition of RANKL, osteoclast activity isn’t downregulated
What is the utility of adding progesterone to hormone therapies?
Progesterone is added to reduce estrogen-induced tumour incidence
What is the mechanism of action for SERMs?
They are non-hormonal, but they mimic the actions of estrogen. Inhibit RANKL production, ensure normal osteoclast activity.
Review slide 25 to see how estrogen has an effect on bone cells
What are some other non-estrogen hormone treatments for osteoporosis?
Calcitonin inhibits bone resorption by osteoclasts (bone remodelling cells) and promotes bone formation by osteoblasts. Not very effective though. Used when other treatments not tolerated
PTH activates osteoblasts, but needs to be injected daily. Only effective if short term use, otherwise it will cause increased fracture risk (like bisphosphonates)
Sclerostin inhibitors prevent sclerostin from inhibiting osteoblast maturation. So sclerostin inhibitors promote osteoblast function
What is osteomalacia?
Softening of bones as a result of inadequate mineralization of the organic matrix (caused by vitamin D deficiency)
Known as rickets in kids
What are some causes of Vitamin D deficiency?
Dietary or inadequate sun exposure due to climate or clothing
INadequate metabolic processing and activation of Vitamin D
Disturbances in phosphate metabolism (kidney unable to retain phosphorus)
Should we recommend VItamin D supplements to our patients?
Not needed in most people, only those who have an actual Vitamin D deficiency
What is the pathology of osteomalacia?
Excess nonmineralized osteoid
Bone deformaties
Low serum calcium and phosphorus
What are the consequences of rickets (childhood osteomalacia)?
Bowlegs (bent lower limbs)
Widened costochondral junction (
Bulging forehead
Delayed dentition (late emergence of teeth)
What are some symptoms of osteomalacia?
Bone fractures that happen with very little injury
Muscle weakness
Widespread bone pain, especiallly in the hips
If Ca2+ is exceptionally low, neurological symptoms may present:
Abnormal heart rhythms
Numbness around the mouth
Numbness of arms and legs
Spasms of hands or feet
What is degenerative joint disease (DJD) or also known as osteoarthritis (OA)?
MOst common joint disease (disease of old age)
Osteoarthritis affects larger people more frequently vs. smaller people
Prior injury can predispose patient to osteoarthritis
What are the two classes of osteoarthritis?
Primary: cause unknown or multi factorial
Secondary: related to another disease
What percentage of people over the age of 12 have arthritis?
About 20%
What is the pathology of osteoarthritis?
Damage to joint
Cartilage can become crispy and flake off
BOne grinds against bone (bone damage and erosion)
Pain from inflammation
FIbrosis of supporting tissue
Osteophytes (bony spikes grow and pierce surrounding soft tissue)
What is crepitus?
It is the presence of sounds coming from a joint (not the same as the popping sounds while moving)
What happens in an osteoarthritic hand?
Joint space narrowing of radiocarpal, carpometacarpal joint (less cartilage)
What happens in an osteoarthritic knee?
Asymmetrical breakdown of the cartilage. One side of the knee cartilage is worn down quicker
How can osteoarthritis be managed?
Exercise (improve range of motion, maintain muscle strength, and reducing weight increase)
PT/OT care and assistive devices
Analgesics, NSAIDs, corticosteroids (used for severe acute inflammation or pain), or hylauronic acid (acts as a lubricant)
Surgery (joint replacement)
What is rheumatoid arthritis (RA)?
It is a chronic multi system disease primarily involving the joints
It is characterized by chronic symmetrical inflammatory synovitis, joint destruction, muscle atrophy, and bone destruction
Other body parts affected:
Lungs (fibrosis/nodules), eyes (dry), blood vessels (vasculitis), and skin (ulcers)
Fatigue is a major symptom associated with rheumatoid arthritis?
What is pannus?
It refers to abnormal, hypertrophied synovium, an abnormal tissue that develops in the rheumatic joint
Pannus causes tissue destruction because it releases damaging enzymes, proteins, and acids that break down bone and cartilage
Will acetaminophen on its own be helpful in treating rheumatoid arthritis?
Mast cells are not the only cells involved, the entire immune system and it cells are contributing to inflammation in the joints
What are the stages of rheumatoid arthritis?
Healthy joint
Synovitis
Pannus
Fibrous ankylosis
Bony ankylosis
What is the mechanism of action of hydroxychloroquine in rheumatoid arthritis?
It raises lysosomal pH in antigen presenting cells (ATC), thereby reducing antigen processing efficiency
A reduction in processing efficiency effectively reduces autoimmune attack by reducing presentation of antigen to other immune/inflammatory cells
What is the effect of sulfasalazine in rheumatoid arthritis?
Inflammatory cell function
Inhibition of folate dependant enzymes (DNA replication)
Inhibition of synovial revascularization
Increase in free radical scavenging activity
What is the effect of minocyline in rheumatoid arthritis?
Reduces IL-10, suppresses Band T cells (immune system deregulation)
Reduces nitric oxide synthase (an enzyme that breaks down cartilage)
Synergistic effects with NSAIDs
What is the effect of methotrexate in rheumatoid arthritis?
Inhibits purine and pyrimidine synthesis (inhibition of DNA replication)
Reduces a bunch of interleukins and TNF-alpha (pro-inflammatory cytokines)
What is the difference between osteoarthritis and rheumatoid arthritis in joint stiffness?
In rheumatoid arthritis, the joints are very stifff and remain like this for more than 1 hour after waking
In osteoarthritis, the joints are only transiently stiff for seconds to minutes after waking. Pain gets worse throughout the the day and depending on activity level. Stiffness also occurs after resting and can also last seconds to minutes
What is Ankylosing Spondylitis?
Ankylosing spondylitis is a form of chronic inflammation of the spine and sacroiliac joints
Causes pain and stiffness in and around the spine
Affect young men disproportionately (HL-B27 is present in 90% of cases)
Ligaments are more affected than bones
Can also cause inflammation or injury to other joint and organs like the eyes, heart, lung, and kidneys
What is the pathogenesis of ankylosing spondylitis?
Initial inflammation may be a result of an activation of the body’s immune system (could be due to a bacterial or microbial infection
What is psoriatic arthritis?
IN 30% of psoriasis patients, they will also develop multi-joint arthritis
What are DMARDs?
Disease-modifying anti-rheumatic drugs
These drugs can have oral formulation or parenteral
What are some treatment options for joint pain in psoriatic arthritis?
NSAIDs
Disease-modifying antirheumatic drugs (DMARDs)
Immunosupressants (reduce autoimmune inflammation)
TNF-alpha inhibitors (reduce joint swelling, pain, and stiffness)
What are some newer drugs approved for use in rheumatoid arthritis?
Apremilast (reduces TNF-alpha, IL-23, and interior
Increased anti-inflammatory mediators such at IL-1999
What is sepsis arthritis?
The joints are infected with pyrogens bacteria
Bacterial inflections usually derive from a hematogenous route of spread (ex. Gonorrhea, Stepolococci, pneumonococci).
Two minor sources of infection of the synovial capsule is direct inoculation directly onto the joint (trauma), and contiguous spread (from nearby tissues)
Usually involves one large joint. Synovial membranes become edematous and congested, the joint wills with pus
What is the pathogenesis of osteomyelitis (septic arthritis)?
PAthogens are seeded into the bone
Infection established
Acute inflammatory response
What are the different types of DMARDs?
Conventional DMARDs: methotrexate, sulfasazine, hydroxychloroquine, and leflunomide
Biological DMARDs (biologics): TNF inhibitors, B cell depleting agent, T cell modulator, IL6 inhibitors, and IL-17 inhibitors
Targeted synthetic DMARDs: JAK inhibitors
What are some sources of joint infections?
Hematogenous (through the blood stream): most common
Direct inoculation (bacteria introduced directly into the joint): trauma or bad injection technique
What are the consequences of an untreated joint infection?
Joint destruction
What is osteomyelitis?
It is the infection the bone itself
What is the pathogenesis of osteomyelitis?
Pathogens can become seeded into the bone
Local edema can put pressure on vascular supply, effectively trapping the dead areas (sequestrum)
In response to the inflammatory process, reactive bone is laid (like of like stye formation in osteoarthritis)
The walled off infection may serve as a source off pathogens for a future infection. Need IV antibiotics to treat this type of infection
