1、2014NOF骨质疏松指南解读,江苏省中西医结合医院内分泌代谢病院区,epidemiology,Since NOF first published the Guide in 1999, it has become increasingly clear that many patients are not being given appropriate information about prevention and many patients are not receiving appropriate testing to diagnose osteoporosis or establish
2、osteoporosis risk. Most importantly, many patients who have osteoporosis-related fractures are not being diagnosed with osteoporosis and are not receiving any of the FDA-approved, effective therapies.,Medical Impact,Fractures and their complications are the relevant clinical sequelae of osteoporosis
3、. Fractures may be followed by full recovery or by chronic pain, disability and deathHip fractures are associated with an 8.4 to 36 percent excess mortality within one year, and followed by a 2.5-fold increased risk of future fractures.,Pathogenesis of Osteoporosis-Related Fractures,Risk Assessment,
4、All postmenopausal women and men age 50 and older should be evaluated for osteoporosis risk in order to determine the need for BMD testing and/or vertebral imaging. In general, the more risk factors that are present, the greater the risk of fracture. Osteoporosis is preventable and treatable, but be
5、cause there are no warning signs prior to a fracture, many people are not being diagnosed in time to receive effective therapy during the early phase of the disease.,Others,Gastrointestinal disorders Hematologic disorders Rheumatologic and autoimmune diseaseNeurological and musculoskeletal risk fact
6、ors Miscellaneous conditions and diseases Medications,T-Score,World Health Organization (WHO) 骨质疏松诊断标准,indication,椎体成像,UNIVERSAL RECOMMENDATIONS FOR ALL PATIENTS,Adequate Intake of Calcium,Men 50-70 1000mg,71 1200mgwomen 51 1200 mgThere is no evidence that calcium intake in excess of these amounts c
7、onfers additional bone strength. Intakes in excess of 1,200 to 1,500 mg per day may increase the risk of developing kidney stones, cardiovascular disease and stroke. The scientific literature is highly controversial in this area,Adequate Intake of Vitamin D,Bring the serum 25(OH)D level to 30 ng/ml
8、(75 nmol/L) and a maintenance dose to maintain this level, particularly for individuals with osteoporosis. Many patients with osteoporosis will need more than the general recommendation of 800-1,000 IU per day. The safe upper limit for vitamin D intake for the general adult population was increased
9、to 4,000 IU per day,Treatment of Vitamin D Deficiency,Adults who are vitamin D deficient may be treated with 50,000 IU of vitamin D2 or vitamin D3 once a week or the equivalent daily dose (7,000 IU vitamin D2 or vitamin D3) for 8-12 wks to achieve a 25(OH)D blood level of approximately 30 ng/ml. Thi
10、s regimen should be followed by maintenance therapy of 1,5002,000 IU/d or whatever dose is needed to maintain the target blood level.,Regular Weight-Bearing and Muscle-Strengthening Exercise,Weight-bearing exercise includes walking, jogging, Tai-Chi, stair climbing, dancing and tennis. Muscle-streng
11、thening exercise includes weight training and other resistive exercises, such as yoga, Pilates and boot camp programs. Before an individual with osteoporosis initiates a new vigorous exercise program, such as running or heavy weight-lifting, a clinicians evaluation is appropriate.,Fall Prevention,ma
12、intaining adequate vitamin D levels and physical activity home safety assessment and modification especially when done by an occupational therapist and gradual withdrawal of psychotropic medication if possible. Appropriate correction of visual impairment may improve mobility and reduce risk of falls
13、. Hip protectors may protect an individual from injuring the hip in the event of a fall,Cessation of Tobacco Use and Avoidance of Excessive Alcohol Intake,Advise patients to stop tobacco smoking Recognize and treat patients with excessive alcohol intake,PHARMACOLOGIC THERAPY,Pharmacologic treatment
14、recommendations,After appropriate evaluation: Initiate pharmacologic treatment in those with hip or vertebral (clinical or asymptomatic) fractures. Initiate therapy in those with T-scores 3 percent or a 10-year major osteoporosis-related fracture probability 20 percent based on the U.S.-adapted WHO
15、absolute fracture risk model (FRAX; www.NOF.org and www.shef.ac.uk/FRAX).,U.S. FDA-Approved Drugs for Osteoporosis,bisphosphonates (alendronate, alendronate plus D, ibandronate, risedronate and zoledronic acid)calcitoninestrogens (estrogen and/or hormone therapy), estrogen agonist/antagonist (raloxi
16、fene), tissue-selective estrogen complex (conjugated estrogens/bazedoxifene)parathyroid hormone (PTH1-34, teriparatide)the RANKL inhibitor denosumab.,Bisphosphonates,双膦酸盐,Drug safety,Side effects are similar for all oral bisphosphonate medications and include gastrointestinal problems such as diffic
17、ulty swallowing, inflammation of the esophagus and stomach. All bisphosphonates can affect renal function and are contraindicated in patients with estimated GFR below 30-35 ml/min. Eye inflammation can also occur.,Drug safety,There have been rare reports of osteonecrosis of the jaw (ONJ) with long t
18、erm use of bisphosphonates for osteoporosis, though ONJ is much more common following high dose intravenous bisphosphonate treatment for patients with cancer. The risk of ONJ appears to increase with duration of treatment beyond five years.,Drug safety,Although rare, low trauma atypical femur fractu
19、res may be associated with the long-term use of bisphosphonates (e.g. 5 years of use). Pain in the thigh or groin area, which can be bilateral, often precedes these unusual fractures. For patients with thigh and groin pain, a stress fracture in the subtrochanteric region or femoral shaft of the femu
20、r may be present. Bilateral x-ray of the femurs should be ordered when an atypical femur fracture is suspected, followed by an MRI or a radionuclide bone scan when clinical suspicion is high enough. Surgical fixation is required in some cases whereas medical conservative treatment is appropriate in
21、other cases. Bisphosphonates should be stopped if atypical femur fractures have occurred.,Calcitonin,Calcitonin reduces vertebral fracture occurrence by about 30 percent in those with prior vertebral fractures but has not been shown to reduce the risk of nonvertebral fractures.Drug administration: 2
22、00 IU delivered as a single daily intranasal spray. Subcutaneous administration by injection also is available.,Drug safety,Intranasal calcitonin can cause rhinitis, epistaxis and allergic reactions, particularly in those with a history of allergy to salmon. The FDA has reviewed long-term post marke
23、ting data concerning calcitonin and the very small increase in the risk of certain cancers.,Estrogen/Hormone Therapy (ET/HT),Estrogen/hormone therapy is approved by the FDA for the prevention of osteoporosis, relief of vasomotor symptoms and vulvovaginal atrophy associated with menopause. Women who
24、have not had a hysterectomy require HT, which also contains progestin to protect the uterine lining.,Drug efficacy,The Womans Health Initiative (WHI) found that five years of HT (Prempro) reduced the risk of clinical vertebral fractures and hip fractures by 34 percent and other osteoporotic fracture
25、s by 23 percent,Drug safety,The Womens Health Initiative (WHI) reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis during five years of treatment with conjugated equine estrogen and medroxyprogesterone acetate (Prempro).,Estrog
26、en Agonist/Antagonist (formerly known as SERMs): Raloxifene,Raloxifene reduces the risk of vertebral fractures by about 30 percent in patients with a prior vertebral fracture and by about 55 percent in patients without a prior vertebral fracture over three years. Reduction in risk of nonvertebral fr
27、acture with raloxifene has not been documented.,Raloxifene,Raloxifene is also indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis. Raloxifene does not reduce the risk of coronary heart disease. Drug administration: Available in a 60 mg tablet form
28、to be taken with or without food. Drug safety: Raloxifene increases the risk of deep vein thrombosis to a degree similar to that observed with estrogen. It can also increase hot flashes and cause leg cramps.,Tissue-Selective Estrogen Complex: Conjugated estrogens/ bazedoxifene (Conjugated estrogens
29、paired with estrogen agonist/antagonist),Drug efficacy,Women who suffer from moderate-to-severe hot flashes (vasomotor symptoms) associated with menopause and to prevent osteoporosis after menopause. Significantly increased mean lumbar spine BMD 1.51 percent, increased total hip BMD. 1.21 percent,Dr
30、ug Administration,0.45mg / 20mgonce daily without regard to meals.,Drug Safety:,Side effects include muscle spasms, nausea, diarrhea, dyspepsia, upper abdominal pain, oropharyngeal pain, dizziness and neck pain. Because this product contains estrogen, it is approved with the same Boxed Warning and o
31、ther Warnings and Precautions that have been approved with estrogen products.,Parathyroid Hormone: Teriparatide,Teriparatide is approved by the FDA for the treatment of osteoporosis in postmenopausal women and men at high risk for fracture. It is also approved for treatment in men and women at high
32、risk of fracture with osteoporosis associated with sustained systemic glucocorticoid therapy.,Drug efficacy,Teriparatide reduces the risk of vertebral fractures by about 65 percent and non-vertebral fragility fractures by about 53 percent in patients with osteoporosis, after an average of 18 months
33、of therapy.,Drug Administration,Teriparatide is an anabolic (bone-building) agent administered by 20 g daily subcutaneous injection. Treatment duration is recommended not to exceed 18 to 24 months.,Drug safety:,Side effects include leg cramps, nausea and dizziness. patients with an increased risk of
34、 osteosarcoma (e.g., Pagets disease of bone and those having prior radiation therapy of the skeleton), bone metastases, hypercalcemia, or a history of skeletal malignancy should not receive teriparatide therapy. It is common practice to follow teriparatide treatment with an antiresorptive agent, usu
35、ally a bisphosphonate, to maintain or further increase BMD.,Receptor Activator of Nuclear Factor kappa-B (RANK) Ligand (RANKL)/ RANKL Inhibitor: Denosumab,Denosumab is approved by the FDA for the treatment of osteoporosis in postmenopausal women at high risk of fracture. Denosumab reduces the incide
36、nce of vertebral fractures by about 68 percent, hip fractures by about 40 percent and non-vertebral fractures by about 20 percent over three years. Denosumab is also indicated to increase bone mass in men at high risk of fracture, treat bone loss in women with breast cancer on aromatase inhibitor th
37、erapies and to treat bone loss in men receiving gonadatropin-reducing hormone treatment for prostate cancer who are at high risk for fracture.,Drug administration and safety,Administered by a health professional, 60 mg every six months as a subcutaneous injection. Denosumab may cause hypocalcemia. D
38、enosumab increased the risk of serious skin infections (cellulitis) and skin rash. Denosumab has been rarely associated with the development of ONJ and atypical femur fractures,Sequential and Combination Therapy,Sequential treatment with anabolic therapy followed by an antiresorptive agent is genera
39、lly preferred. Combination therapy with teriparatide and an antiresorptive can be considered in a few clinical settings in patients with very severe osteoporosis such as spine and hip fractures. There are few indications for combining two antiresorptive treatments, but such options could be consider
40、ed in the short-term in women who are experiencing active bone loss while on low dose HT for menopausal symptoms or raloxifene for breast cancer prevention.,Duration of Treatment,All non-bisphosphonate medications produce temporary effects that wane upon discontinuation. In contrast, bisphosphonates
41、 may allow residual effects even after treatment discontinuation. Evidence of efficacy beyond five years is limited, whereas rare safety concerns such as ONJ and atypical femur fractures become more common beyond five years. Since there is no extensive evidence base to guide treatment duration decisions, duration decisions need to be individualized.,Thank you,
