Metabolic Bone Diseases
* a reduction in bone mass found in all metabolic bone diseases
mechanisms: decreased bone formation, inadequate bone mineralization, & increased bone deossification
Causes: osteoporosis, osteomalacia, malignancies, & endocrine disorders (hyperthyroidism, hyperparathyroidism)
What is osteopenia ?
process of skeletal maintenance after skeletal growth is complete by a 4 month long cycle of bone resorption of osteoclasts and bone formation by osteoblasts; contributes to calcium & phosphate homeostasis
What is bone remodeling?
Rapid onset caused by exercise, viral infections, physical deconditioning/exercise intolerance
may serve as a protective function
What is acute fatigue?
common chronic autoimmune systemic disease (T-cell mediated response that damages connective tissue/synovial membrane [joints])
*affects all ethnic groups (1-2% of the population)
*biologic females 3x > biologic males
*unknown cause with strong genetic predisposition
Occurs 50-75 years of age
What is Rheumatoid Arthritis?
chronic systemic inflammatory autoimmune disease that affects any/all organ systems
more common in females
unknown cause
IgG + IgA; type III hypersensitivity reaction
defective elimination og hyperactive B cells
KEY FINDINGS: facial rash, arthralgias/arthritis, renal disorder, cardiovascular disease; 4+ findings = SLE
DIAGNOSIS: 4+ findings = SLE, elevated Antinuclear antibodies (ANA), Anti-DNA > ANA, CBC
Treatment: management of symptoms + NSAIDs, hydroxychloroquines, corticosteroids, immunosuppressive drugs
What is systemic lupus erythematosus?
*decreased bone density & strength due to loss of mineralized bone mass
*menopause --> increase cytokine --> low estrogen levels --> increased RANKL and decreased OPG --> bone resorption > bone formation
*Risk Factors: CALCIUM (calcium & Vitamin D intake low, Age >50, Lifestyle [ETOH, smoking, sedentary, etc]), caucasian/white women, inherited, underweight, medications [corticosteroids, anticonvulsants])
*Manifest: skeletal fracture (hips, spine, wrist), decreased height b/c of collapsed vertebrae, kyphosis
Treatment: biphosphonates & hormone therapy (estrogen, progestin, testosterone)
What is osteoporosis ?
protein + mineral components removed = tunnel in the osteon
* soluble factors recruit osteoblastsWhat s bone resorption?
*differs in terms of onset, intensity, perception, duration, & relief
What is Chronic Fatigue?
HLA on MHC II + immune trigger
antibody/antibody complex --> complement activation
excess cytokine production (TNF, IL-1)
angiogenesis --> proliferation of synovial cells
pannus invasion --> irreversible damage
neutrophils activated in synovial fluid, inflammatory cytokines induce enzymatic breakdown of cartilage & bone
T-cells use TNF-a to interact with synovial fibroblasts to convert synovium into pannus
What is the pathophysiology of rheumatoid arthritis ?
chronic, multi-systemic inflammatory disease of joints of the axial skeleton (spine+ sacroiliac joints); UNKOWN CAUSE + autoimmune response (lymphocytes/monocytes)
*pain +progressive stiffening of spine [lower back pain when laying down/resting, Kyphosis, hip joint degeneration, #1 = acute anterior uveitis/ocular issues, weight loss, fever, fatigue] aka SPONDY
What is Ankylosing Spondylitis (AS)?
Inadequate mineralization of bone caused by insufficient calcium absorption & phosphate deficiency
* most common amongst elderly due to dietary calcium + vitamin D deficiencies
*renal rickets; inability to activate vitamin D & reabsorb phosphate due to renal failure
CHILDREN: failure/delay in calcification of cartilaginous growth plates in children (types: nutritional, vitamin D-dependent, vitamin resistant)
MANIFEST: bone pain/tenderness + predisposition to pathologic fractures
Treatment: treat underlying cause, vitamin D + calcium supplements, more sunlight exposure
key player are osteoblasts which are bone marrow stromal stem cells that deposit organic matrix (osteoid) on the wall of osteon canal
What is bone formation?
Disabling fatigue for > 6 months
self-reported, non-specific symptoms
etiology unknown
Criteria: severe mental/physical exhaustion --> significant decreased in premorbid activity level
What is Chronic Fatigue Syndrome/Mylagic Encephalomyelitis?
Insidious onset w/ inflammation, fever, fatigue, weakness, anorexia, weight loss, & generalized aching/stiffness
painful/tender/stiff joints
Boutonniere's deformity
Rheumatoid nodules: collection of inflammatory cells around central core of necrosis surrounded by doughy or spongy infiltrate
Ulnar deviation
What is are the clinical manifestation of Rheumatoid Arthritis ?
slow, progressive destruction of the articular cartilage of weight-bearing joints
most prevalent form of arthritis that increases w/age; leading cause of disability/pain
Characteristics: inflammation, degeneration, new bone formation of joint margins, subchondral bone changes, variable degrees of mild synovitis, thickened joint capsule, bouchard's node, Heberden's node
*wear & tear
*osteophyte formation: bony outgrowths (spurs)
What is osteoarthritis (OA)?
2nd most common bone diseases
*onset in 40s
* local areas of excessive bone turnover, disorganized osteoid formation
* mosaic pattern with cement lines; bone marrow fibrosis + increased vascularity in lesions -->weak, brittle bones that cannot support weight --> bowing + fractures
Manifest: (a)symptomatic, lesion(s) in multiple different bones, Skull (HA, tinnitus, vertigo, hearing loss), Kyphosis, pain/stiffness/fractures, cardiovascular disease/heart failure, decreased ventilatory capacity, & mental deterioration
What is Paget Disease?
osteoblasts mediate osteoclast activity via the release of RANKL (receptor of kappa-B ligand) which induces osteoclast activity
RANK: receptor for RANKL found on osteoclast by where binding of RANKL to RANK promotes osteoclast differentiation & proliferation
OPG (osteoprotegerin): blocks actionof RANKL
What is control of bone metabolism & remodeling?
uric acid crystals deposited in joint cavities/connective tissues due to ↓ excretion or ↑ production of uric acid (hyperuricemia)
Linked to purine metabolism
*RISK FACTORS: males, 40-50 y/o, diet (↑ intake organ meats, ETOH, red meat, seafood, & high fructose corn syrup), thiazide diuretics
Manifest: GOUTS (gouty arthritis/monoarticular, onset of renal disease, uric acid ↑, tophi★, stone/renal calculi)
What is Rheumatic disorder: Gout?
based on H&P
Lab tests: anti-citrullinated protein antibody (ACPA), rheumatoid factor (RF),
Presence of C-reactive protein
Duration of symptoms
Erythrocyte sedimentation rate (ESR) + decreased Hb & Hct
What is diagnosis of Rheumatoid Arthritis?
1. damage/death of chondrocytes --> cracks in articular cartilage
2. influx of synovial fluid promotes further cartilage loss
3.cartilage gradually worn away due to synovial fluid influx -> deeper crack
3. new blood vessels grow in from epiphysis & fibrocartilage is deposited
4. fribrocartilage plug cannot support weight-bearing function of cartilage --> wear away & exposes subchondral bone plate --> thickness & sclerosing
5. further cracking --> subchondral bone cyst forms + influx of synovial fluid
6. regrowth of articular surface --> osteophyte formation (bone spur)
What are the stages of osteoarthritis (OA)?
acute: NSAIDs, corticosteroids, colchicine
manage hyperuricemia
what is prevention and treatment of gout ?
precipitation of crystallized uric acid in joints that causes an inflammatory response (tophi)
Acute: triggered by ETOH, ▲ serum uric acid, recurrent
4 phases: asymptomatic/hyperuricemia, acute gouty arthritis, intercritical gout, & chronic tophaceous gout (tophi)
Early pharmacologic therapy, patient education, confirmed diagnosis (DMARDS)
What is the treatment for Rheumatoid Arthritis?
Joint pain (↑ w/ activity), stiffness (↓ w/ activity), enlargement of joint [crepitus], limited ROM/muscle wasting/deformity aka OSPEO
Resolved with tylenol, NSAIDs, corticosteroid injections, surgery