英文医学课件资料：Osteoporosis

1、 Basic bone physiology Osteoclast express CSF1R (M-CSF Receptor) and RANK. Attach to stromal/osteoblastic cells. Osteoblasts express membrane- bound and soluble M-CSF, membrane-bound RANKL, and OPG under the influence of stimulators of resorption (i.e., PTH, 1,25-Vit D, IL-1, TNF, IL-6, IL-11, or PG

2、s). If osteoblastic cells produce more RANKL than OPG, osteoclasts are formed and activated, which increases bone resorption. If osteoblastic cells produce more OPG than RANKL, OPG binds the available RANKL, and new osteoclast formation is prevented. During states of inflammation, T lymphocytes are

3、activated and produce membrane-bound and soluble RANKL, which can stimulate osteoclast-mediated bone resorption. Osteoblast osteoclast interactions Osteoclasts attach to bone by means of podosomes containing 3 integrin. Protons are generated through the actions of carbonic anhydrase II (CAII), which

4、 is transported into the resorption space by the vacuolar-type H+-ATPase proton pump. A chloride channel coupled to the proton pump facilitates charge neutrality across the membrane. Passive exchange of chloride (Cl) for bicarbonate (HCO3) in the basolateral membrane removes excess bicarbonate. Cath

5、epsin K is an important enzyme for the removal of the organic components of bone in the acid environment of the resorption space. The activation of the Wnt signalling pathway leads to an increased proliferation and differentiation of osteoblastic precursor cells, which favours the deposition of new

6、bone and an increase of bone density. Wnt signalling is triggered when the appropriate Wnt peptide binds to a coreceptor complex at the osteoblast cell membrane involving low-density lipoprotein receptor-related protein (LRP) 5 or-6 and the Frizzled (Fz) receptor. Sclerostin interacts with LRP5 and

7、LRP6 and inhibits the binding of Wnt to its receptor, thus blocking bone formation. Sclerosteosis is an AR disorder characterized by bone overgrowth, most prominent in the skull, Mandible. van Buchem disease is also an autosomal recessive skeletal disease characterized by bone overgrowth. Excessive

8、bone formation is most prominent in the skull, mandible, clavicle, ribs and diaphysis of long bones and bone formation occurs throughout life. Bone mass in older adults equals the peak bone mass achieved by age 1825 minus the amount of bone subsequently lost. Peak bone mass is determined largely by

9、genetic factors, with contributions from nutrition, endocrine status, physical activity, and health during growth. The process of bone remodelling that maintains a healthy skeleton may be considered a preventive maintenance program, continually removing older bone and replacing it with new bone. Bon

10、e loss occurs when this balance is altered, resulting in greater bone removal than replacement. The imbalance occurs with menopause and advancing age. The loss of bone tissue leads to disordered skeletal architecture and an increase in fracture risk. Changes within cancellous bone as a consequence o

11、f bone loss. Trabecular bone is lost, leaving an architecturally weakened structure with significantly reduced mass. Cosman et al. Osteoporosis int. 2014 Osteoporosis is a silent disease until it is complicated by fractures. These fractures occur following minimal trauma or, no trauma. Fractures are

12、 common and place an enormous medical and personal burden on the aging individuals who suffer them. Take a major economic toll on the nation. Osteoporosis can be prevented, diagnosed, and treated before fractures occur. Even after the first fracture has occurred, there are effective treatments to de

13、crease the risk of further fractures. The National Osteoporosis Foundation (NOF) estimates that 10.2 million Americans have osteoporosis and that an additional 43.4 million have low bone mass. More than 2 million osteoporosis- related fractures occur annually in the U.S., more than 70% of these occu

14、r in women. ENDOCRINE PRACTICE Vol 22, 2016 In men- 50 year old and older with clinical risk factors or fragility fracture. Treatment Other contraindications to oral bisphosphonate administration include the inability to follow the dosing regimen for oral use (i.e., inability to remain upright for 3

15、0-60 minutes), the presence of anatomic or functional esophageal abnormalities that might delay tablet transit (e.g., achalasia, stricture, or dysmotility), and the presence of documented or potential GI malabsorption (e.g., gastric bypass procedures, celiac disease, Crohns disease, infiltrative dis

16、orders, etc.). ONJ was first reported in patients with advanced cancer receiving high-dose bisphosphonate and Denosumab therapy (X10 than in osteoporosis). AFF of the subtrochanteric region is another rare event that seems to be increased with long-term bisphosphonate therapy (5 years duration). A r

17、epresentative case A 56 year old women. Previous heavy smoker. Early menopause (age 40). Severe COPD. Crohns disease. Low 25(OH)-Vit D level. Chronic prednisone treatment. Osteoporosis Dx- 2009 Osteoporosis treatment: 2009-2012- Oral BP 2012-2013- Teriparatide (1Y) 2013- 06/2015- Oral BP P value Atypical hip fractures N= 19 Typical hip fractures N= 589 0.00714 (73.7%)250 (42.5%)Any BP exposure, N (%) 0.00382 (59;145)42 (9;92)Total Duration of BP exposure, Month, Median (Q1;Q3) 0