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Primary hyperparathyroidism can cause osteoporosis. The core mechanism by which PHPT leads toosteoporosis is the overproduction of PTH, which persistently stimulatesincreased osteoclast activity, resulting in enhanced bone resorption. This, inturn, causes bone loss and decreased bone mineral density. -------- milk-alkali Excessive intake of calcium and absorbablealkali (e.g., calcium carbonate preparations used in patients withosteoporosis) and the resulting hypercalcemia cause renal vasoconstriction anddecreased glomerular blood flow. In addition, inhibition of the Na-K-2Clcotransporter (due to activation of calcium-sensing receptors in the thickascending loop) and impaired antidiuretic hormone activity lead to loss ofsodium and free water. This results in hypovolemia and increased reabsorptionof bicarbonate(due to RAAS) (augmented by the increased intake of alkali). It also leads to hypophosphatemia (due tointestinal binding of phosphate by calcium carbonate) and hypomagnesemia (dueto decreased renal reabsorption of magnesium). ---------------------- Osteoporosis+HTN Use thiazide --------------- Corticosteroid can cause osteoporosis (cushing syndrome as well) ------------------------- Osteoporosis + palpable vertebral step-off +pinpoint tenderness+Onset following minor trauma =compression fracture ------------- 1. Effects of Estrogen on BoneMetabolism ✅ Inhibitsosteoclast activity → Reduces bone resorption, preventing bone loss.
✅ Promotesosteoblast function → Enhances bone formation, maintaining bonestrength.
✅ Decreasesbone turnover rate → Preserves bone mineralization balance, reducingmicrostructural damage.
✅ Reducesinflammatory factors (IL-6, TNF-α, RANKL) → Prevents bone loss. 2. How Estrogen Deficiency Leads toOsteoporosis 🚫 Postmenopausalestrogen decline → Increased osteoclast activity, decreased osteoblastfunction → Bone resorption > Bone formation → Rapid bone loss,increasing osteoporosis risk.
🚫 Long-termestrogen deficiency (e.g., amenorrhea, ovarian failure) → Decreased bonemineral density (BMD), increasing the risk of fragility fractures (e.g.,hip, vertebrae, wrist). -------------------------------- USPSTF recommendsdual-energy X-ray absorptiometry (DEXA) for osteoporosis screening.Women aged 65 years or older should undergo screening, as it is a GradeB recommendation. For women under 65 years old, screening is alsorecommended if they have a high risk of fractures, which can be assessedusing the FRAX score. ------------ Hyperthyroidism can cause osteoporosis/↑ fracture rate (due to T3directly stimulates bone resorption) -------- Prolactinomas can lead to reduced estrogenlevels, which may cause osteoporosis in females. ------------------------- Turner syndrome leads to osteoporosis dueto estrogen deficiency from ovarian dysfunction, which impairsbone mineralization and increases bone resorption. ----------------- These conditions contribute to osteoporosisthrough different mechanisms, primarily by increasing bone resorption,decreasing bone formation, or disrupting calcium-phosphorus metabolism. 1. Hypogonadism Mechanism:
- Deficiency of sex hormones (testosterone, estrogen) → Increases osteoclast activity, reduces osteoblast function.
- Testosterone can be converted to estrogen, which plays a crucial role in bone health in both men and women.
- Low estrogen levels (e.g., in postmenopausal women and men with low testosterone) lead to rapid bone loss.
2. Chronic Kidney Disease (CKD) Mechanism:
- Impaired vitamin D activation → Decreased 1,25-(OH)₂D → Reduced calcium absorption → Secondary hyperparathyroidism (SHPT).
- Elevated parathyroid hormone (PTH) stimulates osteoclasts, leading to bone resorption and renal osteodystrophy.
- Hyperphosphatemia suppresses active vitamin D synthesis, further impairing bone mineralization.
3. Chronic Liver Disease Mechanism:
- Vitamin D metabolism disorder: The liver is responsible for 25-hydroxylation of vitamin D. Liver disease leads to vitamin D deficiency → Calcium-phosphorus imbalance.
- Reduced protein synthesis affects bone matrix formation (e.g., osteocalcin, type I collagen).
- Chronic inflammation (e.g., cirrhosis) → Pro-inflammatory cytokines (TNF-α, IL-6) inhibit osteoblast function.
- Disrupted sex hormone metabolism → Further affects bone turnover.
4. Inflammatory Disorders (e.g.,Rheumatoid Arthritis, RA，Ankylosing spondylitis) Mechanism:
- Inflammatory cytokines (TNF-α, IL-1, IL-6) stimulate osteoclasts, increasing bone resorption.
- Chronic inflammation inhibits osteoblast activity, impairing new bone formation.
- Long-term corticosteroid use (for RA and other inflammatory diseases) leads to glucocorticoid-induced osteoporosis.
- Reduced physical activity (due to joint pain) decreases mechanical stimulation of bones, further promoting bone loss.
5. Multiple Myeloma (MM) Mechanism:
- Myeloma cells release RANKL, stimulating osteoclast activity, leading to excessive bone resorption and lytic lesions.
- Inhibition of osteoblast differentiation → Impaired bone formation.
- Suppression of normal hematopoiesis in the bone marrow affects bone metabolism.
- Chronic inflammation and overexpression of IL-6 further accelerate bone loss.
6. Alcoholism Mechanism:
- Directly inhibits osteoblasts, reducing bone formation.
- Increases osteoclast activity, accelerating bone resorption.
- Malnutrition: Deficiencies in vitamin D, calcium, and protein contribute to impaired bone health.
- Affects sex hormone levels: Alcohol reduces testosterone and estrogen levels, negatively impacting bone density.
- Liver damage from chronic alcohol use further impairs vitamin D metabolism.
7. Immobilization (Prolonged Bed Rest orReduced Activity) Mechanism:
- Lack of mechanical stimulation reduces bone remodeling (Wolff’s Law).
- Increased osteoclast activity, decreased osteoblast function due to disuse.
- Increased calcium loss in urine → Hypercalcemia may suppress PTH, further impairing bone metabolism.
Summary: Common Mechanisms ofOsteoporosis in These Conditions Condition Primary Mechanism Leading to Osteoporosis
Hypogonadism Low sex hormones → Increased osteoclast activity
Chronic Kidney Disease (CKD) Vitamin D deficiency, secondary hyperparathyroidism
Chronic Liver Disease Vitamin D metabolism impairment, inflammation
Inflammatory Disorders (e.g., RA) Pro-inflammatory cytokines stimulate osteoclasts, corticosteroid use
Multiple Myeloma (MM) Myeloma cells release RANKL → Excessive bone resorption
Alcoholism Direct inhibition of osteoblasts, malnutrition, hormone imbalance
Immobilization Lack of mechanical stimulation → Increased bone resorption These conditions promote boneresorption, suppress bone formation, and alter calcium-phosphorus homeostasis,leading to osteoporosis and an increased risk of fractures. ----------------------- Bisphosphonates (e.g., alendronate,risedronate) -First-line TX for most F withpostmenopausal osteoporosis but are contraindicated in renal failure. -Bone density is typically rechecked after2 years to assess treatment response. -Due to the risk of atypical fractures withprolonged use, treatment is usually discontinued after 5 years. Bisphosphonate-related osteonecrosis ofthe jaw (ONJ)
- Bisphosphonate-related osteonecrosis of the jaw (ONJ) is most common in cancer patients receiving high-dose intravenous bisphosphonates but can also occur in those taking oral bisphosphonates for osteoporosis.
- Classic presentation: Exposed necrotic bone following tooth extraction or other dental procedures, which may persist for months to years and is often asymptomatic.
- Common site: The mandible is more frequently affected than the maxilla.
- Treatment: Primarily supportive, including oral hygiene care and antibacterial rinses; oral antibiotics and limited debridement are used only when necessary.
- Prevention: Due to the potentially intractable course, dental consultation and completion of any anticipated dental procedures are recommended before initiating bisphosphonate therapy.
-------------- Paget disease is the mc bone disorder afterosteoporosis, affecting approximately 3% of adults age >40. -------------- ？Osteoporosis prevention <30 yo==》exercise >30 yo==》quit smoking ---------------------- ？RF for osteoporosis Age>gender>Caucasian race ？Low BMI ----------- Tx with teriparatide（recombinant PTH analog） for more than 2years can be considered in some patients with a high fracture risk --------- nasal calcitonin can treat Osteoporosis and reduce risk of vertebralfractures （Long-term use may increase the risk ofcancer: The FDA has warned that prolonged use of calcitonin may increase therisk of malignant tumors, leading to certain restrictions on its use.）
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发表于 2025-2-27 09:24:07