Fibromyalgia & Osteoporosis Class Notes PDF

Fibromyalgia *Syndrome of chronic, widespread pain and tenderness* **Common Concomitant Symptoms** Fatigue Non-restorative sleep Cognitive difficulties [Risk Factors] Sex - 90% female Age - 30 to 50 years old Rheumatic disease -- may co-occur with RA, SLE, or osteoarthritis Genetics/family...

Fibromyalgia *Syndrome of chronic, widespread pain and tenderness* **Common Concomitant Symptoms** Fatigue Non-restorative sleep Cognitive difficulties [Risk Factors] Sex - 90% female Age - 30 to 50 years old Rheumatic disease -- may co-occur with RA, SLE, or osteoarthritis Genetics/family history [Triggers/Precipitating Factors] Viral illness Chronic fatigue syndrome HIV Lyme disease Physical or emotional trauma/stress, acute illness Steroid withdrawal [Pathophysiology] **Abnormal pain processing** Source of sensory input is unknown Altered pain threshold and pain tolerance (augmentation) **\ ** **Alterations in mood/anxiety** Deficiencies in serotonin leads to depression and anxiety **Alterations in autonomic nervous system function** Decreased baroreceptor/vasoconstrictive responses -- difficulty with BP regulation, dizziness, may contribute to fatigue Lower heart rate variability -- may contribute to fatigue, sleep disturbances, and other physiological consequences **Hormonal Abnormalities** Decreased levels of growth hormone and insulin-like growth factor (IGF-1) Hypothalamic-pituitary axis abnormalities **Abnormal sleep cycle** Alpha wave intrusion during delta wave sleep -- correlated to poor sleep and decreased GH/IGF-1 levels Poor sleep is highly correlated to increased pain [\ ] [FYI - Clinical Manifestations] Pain and Tenderness - persistent, widespread, and diffuse; hypersensitivity to touch Fatigue - worse upon awakening and mid-afternoon Sleep disturbances - difficulty falling asleep or staying asleep; tired upon awakening Cognition difficulties - memory deficits, forgetfulness, confusion, inability to concentrate Migraines or tension headaches Depression and anxiety Irritable bowel syndrome Overactive Bladder Pelvic Pain Temporomandibular joint syndrome Restless leg syndrome Osteoporosis *A progressive bone disease whereby bones lose density, become thin, brittle and prone to fracture.* [Histology Review -- Bone Tissue] **Cells** Osteoblasts Osteocytes Osteoclasts **Extracellular Matrix** Minerals -- calcium and phosphorus (hydroxyapatite) Collagen fibers [Risk Factors] **Non-Modifiable** Age \> 65 years Female sex - 70% females (overall) Ethnicity - Caucasians and Asians at higher risk Small stature, low body weight Genetics/Family history - family history of osteoporotic fractures **Endocrine** Menopause or surgical removal of ovaries leading to estrogen deficiency Low levels of testosterone (hypogonadal conditions, andropause, etc.) **Dietary** Calcium deficiency Vitamin D deficiency Excessive alcohol intake Anorexia/bulimia **\ ** **Lifestyle** Lack of weight bearing activity (especially during the first two decades when peak bone mass is achieved) Smoking **Medications** Corticosteroids (prednisone, hydrocortisone) Anticonvulsants (phenytoin) Loop diuretics (furosemide) Others: methotrexate, heparin, PPIs, Depo-Provera, levothyroxine [Types] Primary type 1 -- occurs in females after menopause Primary type 2 (senile osteoporosis) -- occurs in males and females over age 75 years (M:F ratio = 1:2) Secondary osteoporosis -- due to other diseases and/or medications [\ ] [Pathophysiology] **Overview - Alterations in bone remodeling** With aging (and under the influence of other factors), osteoclast activity exceeds osteoblast activity Bone resorption increases in conjunction with inadequate formation of new bone during remodeling Consequence: Bone density decreases **Role of RANKL/RANK in bone remodeling** *RANKL = receptor activator of nuclear faculty ~K~B ligand* *RANK = receptor activator of nuclear faculty ~K~B* RANKL is a signaling molecule is released by osteoblasts (and other cells) RANKL activates osteoclasts by binding to RANK, a receptor on osteoclasts Normally, RANKL activity increases osteoclastic activity and bone resorption Increased RANKL/RANK activity can lead to osteoporosis **\ ** **Role of osteoprotegerin (OPG)** OPG is a decoy receptor for RANKL on the osteoblasts Normally, RANKL binds to OPG instead of RANK on the osteoclasts and prevents osteoclastic activity Deficiencies in OPG can lead to increased RANKL stimulation of osteoclasts and bone resorption/bone loss **Role of testosterone and effects of testosterone deficiency** Testosterone is converted to estrogen to help build bone mass Testosterone also inhibits bone resorption Testosterone deficiency can lead to reduced bone formation **Role of estrogen and effects of estrogen deficiency** *Estrogen plays a role in bone growth in both males and females. During puberty estrogen stimulates the release of growth hormone which stimulates bone growth. Estrogen is also required for epiphyseal growth plate fusion.* Estrogen stimulates OPG secretion which prevents osteoclastic effects of RANKL Estrogen exerts an anti-apoptotic effect on osteoblasts Estrogen exerts a pro-apoptotic effect on osteoclasts Decreased estrogen increased RANKL and increased osteoclast activity increased bone resorption/bone loss [Clinical Consequences] **Bone fractures** Often the first manifestation Occur after minor trauma Types: Hip, spine compression, rib **Kyphosis and other spinal abnormalities** Height loss Back pain Nerve impingement Impaired physical function