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Description : This medical presentation titled "Osteoporosis - Bad to the Bone" provides us definition and demographics of osteoporosis, its risk factors, its diagnosis, information on secondary osteoporosis, its treatment options, and some guidelines for follow-up.

Tags : Osteoporosis, Bone, definition, demographics, risk factors, diagnosis, secondary osteoporosis, treatment options, guidelines, skeletal disorder, bone strength, risk of fracture, low bone mineral density, BMD, Fragility fracture, trauma, Bone remodeling, Pathophysiology

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Slide 1-

Osteoporosis: “Bad to the Bone” Mary Warden, MD
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Outline Definition and demographics Risk factors Diagnosis Secondary osteoporosis Treatment options Guidelines for follow-up
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Definition of Osteoporosis “Osteoporosis is defined as a skeletal disorder characterized by a compromised bone strength predisposing a person to an increase risk of fracture.” NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. JAMA. 2001;285:785-795
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Definition of Osteoporosis Diagnosed on basis of either a health outcome (low-impact or fragility fracture) or an intermediate outcome (low bone mineral density—BMD) Low-impact fracture: one that occurs after a fall from standing height or less Fragility fracture: occurs spontaneously or with no trauma (cough, sneeze, sudden movement)
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Bone Remodeling Bone remodeling occurs throughout life. At a given time, different sites on the bone surface will be in different stages of the remodeling process. Activation stage: cells on bone surface retract. Resorption stage: osteoclasts remove bone, forming a resorption pit. Formation stage: osteoblasts fill the pit with new collagen matrix. Mineralization stage: matrix is mineralized to form new bone.
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Pathophysiology of Osteoporosis Osteoporosis occurs when normal balance is upset and bone resorption exceeds formation, resulting in a net loss of bone tissue with associated changes in bone architecture. Such an imbalance can occur with the onset of menopause, where diminishing estrogen levels lead to excessive bone resorption that is not fully compensated for by an increase in bone formation.
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A Major Health Threat in the US 4-6 million women have osteoporosis. 18 million people have low bone mass. 1 to 2 million men have osteoporosis 8 to 13 million men have low bone mass. 40 -50 % of females aged 50 years or older are at risk for developing an osteoporosis-related fracture during their lifetime. Ettinger, M. Arch Intern Medicine.2003;163:2237-45.
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Osteoporosis and Fractures Adapted from Ettinger, M. Arch Intern Medicine.2003;163:2237-45.
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Outcomes of Hip Fractures 24% excess mortality in 12 months 50% do not recover baseline function 25% require long-term nursing home care 33% will fracture the opposite hip Ray, N.F. et al. J. Bone Mineral Res. 1997;12:24-35 Consensus Develop. Conf., Am. J. Med. 1993;94:646-650 Riggs, B.J. and Melton, L.J. Bone 1995;17:505S-511S
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Outcome of Vertebral Fractures Kyphosis Loss of height Pain Loss of independence and mobility Compression of organs leading to pain, reflux, incontinence, and difficulty breathing.
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First Case T. W. is a 61 year old postmenopausal woman comes to establish care. PMHx: HTN, Hyperlipidemia Meds: Hctz, Lipitor SHx: Smokes 1 ppd FHx: Mother DM, Father Colon CA HCM: Colonoscopy 5 yrs ago, Mammo/pap 6 mon ago PExam: 120/80 normal Recent labs: Chol 180, LDL 100, Trig 150, and HDL 50
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She primarily came for refills on her medication. What else would be important to do for this 61 year old female?
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Risk Factors for Osteoporosis and Related Fractures Major Risk Factors Personal history of fracture as an adult History of fragility fracture in first degree relative Low body weight (<127 lbs) Current history of smoking Use of oral corticosteroids for more than 3 months Additional Risk Factors Impaired vision Estrogen deficiency Poor health/ fragility Recent falls Low calcium intake (lifelong) Low physical activity Excessive use of alcohol (more than 2 drinks/ day) National Osteoporosis Foundation. Available at http://www.nof.org/physguide.
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Further questioning and examination…. The patient reports …. She has never liked diary products and rarely takes calcium. She went through menopause at the age of 55. Last year her mother suffered a hip fracture. Her weight is 123 lbs Her height is 5’4” ( loss of ½ inch) Both men and women experience an age-related decline in BMD starting in midlife. Women experience more rapid bone loss in the early years following menopause
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Risk Factors for Osteoporosis and Related Fractures Major Risk Factors Personal history of fracture as an adult History of fragility fracture in first degree relative Low body weight (<127 lbs) Current history of smoking Use of oral corticosteroids for more than 3 months Additional Risk Factors Impaired vision Estrogen deficiency Poor health/ fragility Recent falls Low calcium intake (lifelong) Low physical activity Excessive use of alcohol (more than 2 drinks/ day) *This patient has several risk factors for osteoporosis.
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Indications for Bone Mineral Density (BMD) Testing Women age 65 and older regardless of additional risk factors. Postmenopausal women under age 65 with risk factors (low body weight, family history of fractures) All adults with a fragility fracture. Men age 70 or older Adults with a disease or condition associated with low bone mass or bone loss. Adults taking medications associated with low bone mass/ bone loss. Any person considering pharmacological therapy or anyone being treated. Position Statement for International Society for Clinical Densitometry. J Clin Endo Meta, Aug 2004, 89(8):3651-55.
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Assessing BMD: Dual Energy X-ray Absorptiometry (DXA) Central DXA with measurements at the posteroanterior lumbar spine, femoral neck or total hip is the “gold standard” for diagnosing osteoporosis. Central DXA provides reproducible results at important sites for osteoporosis fractures. Lateral spine should not be used for diagnosis but may have a role in monitoring. Forearm BMD (33% distal radius of the nondominant forearm) should be measured when the spine and/ or hip cannot measured or interpreted. Spine BMD tend to increase with degenerative arthritis and should be interpreted with caution in the elderly.
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Assessing BMD: Other Techniques Quantitative computed tomography can analyze trabecular and cortical bone separately and is sensitive to early bone loss in the vertebrae. Application of T-scores to predict the risk of fracture with the use of CT has not been validated. More costly and more radiation. Peripheral DXA, calcaneal ultrasonography, single or dual-photon radionuclide absorptiometry may be useful for assessing risk of fracture. Not recommended for diagnosis and management of osteoporosis.
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Comparison of Bone Densitometry by Charge Adapted from Cummings et al. JAMA, Oct 2002, 288(15), 1889-97.
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T Scores and Z Scores T Scores Number of standard deviations (SDs) from the mean bone density values in normal sex-matched young adults. Used to make the diagnosis of osteopenia and osteoporosis. Z score Number of SDs from the normal mean bone density value for age- and sex-matched controls. If lower than -2.0 may suggest presence of a secondary cause of osteoporosis. Used to assess bone loss in premenopausal females.
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Defining The T-score OSTEOPOROSIS LOW BONE MASS (“OSTEOPENIA”) NORMAL BONE MASS -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -.5 0 +.5 +1 T-score
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T. W. is sent for a DXA and the T-score results are… - 2.8 at the hip- 2.4 at the spine
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This patient has osteoporosis. OSTEOPOROSIS LOW BONE MASS (“OSTEOPENIA”) NORMAL BONE MASS -4.0 -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -.5 0 +.5 +1 T-score Note: Use the lowest BMD measurement to make the diagnosis.
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Indications for Treatment of Postmenopausal Osteoporosis National Osteoporosis Foundation: T score below -2.0 with no risk factors T score below -1.5 with one or more risk factors Prior vertebral or hip fracture American Association of Clinical Endocrinology: T score < - 2.5 T score < -1.5 and risk factors Low trauma fracture and low BMD NOF: http://www.nof.org. Hodgson SF et al. Endocr Pract 2003;9:544-64.
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Evaluation of Osteoporosis Comprehensive history and physical examination Baseline labs: CBC Serum chemistry studies( Electrolytes, Ca, Phos, total protein, albumin, liver enzymes, AP, Cr) Urinary calcium excretion AACE Osteoporosis Guidelines
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Causes for Secondary Osteoporosis in Adults
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Other Labs for Secondary Osteoporosis Workup Serum thyrotropin ESR Serum PTH Serum 25-hydroxyvit D Urinary free cortisol and other tests for adrenal hypersection Serum or urine protein electrophoresis Bone marrow aspiration and biopsy Acid- base studies Biochemical markers for bone turnover (Bone specific AP, urine and serum collagen crosslinks) Serum tryptase, urine N-methylhistamine or other tests for mastocytosis AACE Osteoporosis Guidelines, Endo Prac.2003;9(6)545-564.
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T. W. Further examination does not suggest secondary causes of bone loss. Lab studies are all normal. What treatment options are available?
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Nonpharmocologic Treatment Calcium 1000 mg (19 -50 years) 1500 mg (> 50 years) Vitamin D 400 IU/day – 800 IU/day (elderly) Exercise Smoking cessation (smokers tend to be thinner, undergo early menopause, have increased catabolism of endogenous estrogen, experience more fractures) Moderation of alcohol Decrease caffeine
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Effect of Calcium and Vitamin D on Fractures Chapuy et al. 1994 Institutionalized French women given calcium(1200 mg) and Vit D (800IU/day) showed significant reduction Hip fractures OR = 0.73 ( 0.67 – 0.84) Nonvertebral fractures OR = 0.72 (0.60-0.84) Recker et al. 1996 Postmenopausal women with prevalent vertebral fractures given calcium (1200 mg) showed significant reduction Vertebral fractures Placebo 51% Calcium 28% ( p= 0.023) Dawson- Hughes et al. 1997 Healthy independently living postmenopausal women given calcium (500 mg/day) and Vit D (700 IU/day) showed significant reduction Nonvertebral fractures RR 0.4 (0.2-0.8)
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Calcium Calcium supplements should be adjunct – not monotherapy. Calcium carbonate is cheaper but not as bioavailable as calcium citrate. Use calcium citrate in patients who are hypochlorhydric or achlorhydric (including those taking gastric acid-inhibiting drugs) and for patients with history of kidney stones. Common adverse effects of calcium: constipation, bloating, and gas (less with calcium citrate).
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Vitamin D Sufficient vitamin D intake is needed to maintain circulating serum levels of 1,25 dihydroxyvitamin D which are adequate to stimulate calcium absorption. An intake of 400-600 IU of Vitamin D per day is recommended for all adults older than 50. Recommend 800 IU/d for those at risk of deficiency such as elderly, chronically ill, housebound, or institutionalized.
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Pharmacological Interventions Two categories: Antiresorptive agents (reduce bone resorption > promote bone formation) Bisphosphonates Raloxifene Calcitonin Estrogen Anabolic agents (stimulate bone formation) Teriparatide
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Oral Bisphosphonates for Osteoporosis
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Alendronate Number of randomized, clinical trials have demonstrated its effectiveness in increasing BMD and decreasing risk of osteoporotic fractures. Liberman: Differences between Alendronate (10 mg/day) and placebo Increase in BMD (8.8% spine, 5.9 fem neck, 7.8 greater troch). Fewer vertebral fractures ( 3.2 vs 6.2 %). Fracture Intervention Trial – Vert study arm: Increase in BMD (4.1 % femoral neck, 6.2 spine) Risk reduction of vertebral fractures 50% and hip and wrist fractures 30%. Liberman et al. NEJM 1995; 333:1437-1443. Black et al Lancet 1996; 348:1535-1541.
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Risedronate Randomized, clinical trials have demonstrated its effectiveness in increasing BMD and decreasing risk of osteoporotic fractures. VERT trials in North America(NA) and Multinational(MN) -results similar Increase in BMD lumbar spine (4.3-5.9%) and femoral neck (2.8-3.1%) Risk reduction new vertebral fractures 41-49% Risk reduction is new nonvertebral fractures 39% (NA trial- significant) and 33% (MN trial- not significant). Harris et al, JAMA 282: 1344-1352. Reginster et al Osteoporosis Int 11: 83-91.
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Ibandronate Recent FDA approval -dose 2.5 mg daily or 150 mg monthly Oral Ibrandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE)--Placebo vs 2.5 mg vs 20 mg every other day for 12 doses every 3 months Results: Reduction of vertebral fracture: 62% (p=0.0001) and 50%(p=0.0006) Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis (MOBILE)- comparison of 2.5mg/daily vs 150 mg/monthly Results: Increase in BMD lumbar (5.0 vs 6.6 %) Similar results for hip density. No fracture data reported. Chestnut, et al. J Bone Miner Res 2004;19:1241. Reginster et al. Ann Rheum Dis 2006; 65:654-61.
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Bisphosphonates Poorly absorbed—must be taken after overnight fast Contraindicated in severe renal impairment Correct hypocalcemia Proper administration is important to avoid esophageal irritation ( upright position with 8 ounces of water). No eating or drinking for 30 min ( 60 min for Boniva) Side effects: - GI disturbances (heartburn, abdominal pain, esophageal ulcer) - Severe bone, joint and/ or muscle pain - Ocular inflammation - Osteonecrosis of jaw (rare)
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Raloxifene Selected estrogen receptor modulator (SERM) Acts as an ER modulator in the bone and on serum lipid concentrations and ER antagonist on breast and uterine tissue Indications: Treatment and prevention of osteoporosis Recommended dose: 60 mg/ day Side effects: venous thromboembolic disease, hot flashes, leg cramps Ettinger et al. JAMA. 1999;282:637-645.
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MOREMultiple Outcomes of Raloxifene Evaluation Multicenter, double-blind, placebo-controlled trial 7705 postmenopausal women with osteoporosis Randomized to Raloxifene 60 mg/d, 120 mg/d, or placebo Results: Significant reduction in vertebral fractures No significant reduction in nonvertebral fractures Significantly increased BMD vs placebo - 2.6% at lumber spine - 2.1% at femoral neck Ettinger B, et al. JAMA. 1999;282:637-645.
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Calcitonin Slows bone loss by inhibiting osteoclast- mediated bone resorption. Approved for the treatment (not prevention) Dose: 200 IU/day nasal spray 100 IU/day SQ or IM Side effects: rhinitis, epistaxis
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Prevent Recurrence of Osteoporotic Fractures (PROOF) Multicenter, double-blind, placebo-controlled trial 1225 postmenopausal women with low lumbar spine BMD and 1-5 vertebral fractures Nasal spray salmon calcitonin 100, 200, or 400 IU/day, or placebo Results: 36% reduction in vertebral fractures No significant reduction for hip or nonvertebral fractures Chestnut CH et al. Am J Med, 2000;109:267-76.
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Estrogen/ Hormone Therapy Estrogen alone or in combination with progesterone can decrease bone turnover, bone loss, and fractures. Women’s Health Initiative showed mildly increased absolute risk of following serious adverse events: Combination therapy: coronary heart disease, stroke, venous thromboembolism and breast cancer. Estrogen therapy: stroke and venous thromboembolism. Hormone therapy is only approved for the prevention of osteoporosis, not treatment. Anderson et al. JAMA. 2004;291:1701-1712. Cauley et al. JAMA 2003;290:1729-38.
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The patient decides to use alendronate 70 mg weekly.You give her the prescription.Recommend Cal 1500 mg and Vit D 400 IU. Recommend smoking cessation.How and when should you reevaluate the effectiveness of your treatment?
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Monitoring Therapy Serial BMD Inherent variability (precision error). For DXA: Need BMD difference of 3-5 % to be clinically significant in actual BMD reading—gm/cc No change or even slight reduction does not warrant alteration of therapy. AACE Osteoporosis Guidelines, Endo Prac.2003;9(6)545-564.
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Guidelines for Follow-up BMD Measurements “Normal” baseline BMD ( T-score > -1.0): follow-up every 3-5 years (if well above min. acceptable level, may not need any further BMD testing) Patients in osteoporosis prevention program: every 1-2 years until stability documented then every 2-3 years Patients on treatment: yearly for 2 years. If stable after 2 years then every 2 years. Otherwise annual follow-up AACE Osteoporosis Guidelines, Endo Prac.2003;9(6)545-564.
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Second Case TF is a 71 year old woman with a history of two vertebral fractures, “two inch” loss in height and low BMD. She has been taking risedronate 35 mg once weekly along with calcium and vitamin D for 2 years. She recently suffered a hip fracture and required ORIF. DXA last year T-score: -3.0 in the spine -2.7 in the hip Repeat DXA new T- score: -3.5 in the spine -3.2 in the hip
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Are there secondary causes for her osteoporosis and new fracture? Remember to exclude secondary causes. Serum calcium ( hyperparathyroidism) TSH ( hyperthyroidism) 25-hydroxyvitamin D ( Vit D deficiency) 24 hr urinary calcium ( malabsorption of calcium and renal abnormalities) Also consider celiac disease, occult use of glucocorticoids, endogenous Cushing’s disease, and prolonged immobility.
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Is she taking the bisphosphonate and is it being absorbed? Compliance with a once-weekly bisphosphonate may be an issue. Biochemical markers to assess bone turnover/resorption ( example: Urinary N-telopeptide) may suggest noncompliance or incomplete absorption.
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What alternative treatment is available? Options that are available: Prescribe another once weekly bisphosphonate. Change bisphosphonate to raloxifene or calcitonin ( however studies with these medications did not demonstrate reduction in nonvertebral fractures). Offer patient PTH (1-34): Teriparatide
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PTH (1-34): Teriparatide First anabolic agent approved by the FDA for the treatment of osteoporosis. Dose: 20 mcg/day SQ Indications: Postmenopausal women with severe osteoporosis. Men with primary or hypogonadal osteoporosis. Patients with glucocorticoid-induced osteoporosis
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PTH Reduced vertebral and nonvertebral fractures by more than 50%. Significantly increased BMD after 19 months 8.6% at lumbar spine 3.7% at the trochanter Black Box Warning: osteosarcoma in rats. Duration of therapy: should not exceed 2 years. Therapy with bisphosphonate should be discontinued - may blunt the anabolic effect Therapy with reabsorptive agent should be restarted after PTH stopped. Neer RM et al. ,NEJM 2001;344:1434-1441.
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Conclusions Osteoporosis occurs in both women and men (young and old). Manifestations are silent until a catastrophic event occurs. Early identification of risk factors and secondary causes followed by appropriate treatment may reduce the incidence and complications of osteoporosis.
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References: NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. JAMA. 2001;285:785-795 Ettinger, M. Aging Bone and Osteoporosis. Arch Intern Medicine. 2003;163:2237-45. National Osteoporosis Foundation. Available at http://www.nof.org/physguide. Melton LJ, Chrischilles EA, Cooper C et al. Perspective: how many women have osteoporosis? J Bone Miner Res. 1992;7(9):1005-10.
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References: Ray, NF, Chan JK, Thamer M, Melton LJ. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: Report from the National Osteoporosis Foundation. J Bone Miner Res 1997;12:24-35 Consensus Development Conference: Diagnosis, Prophylaxis and Treatment of Osteoporosis. Am J Med 1993;94:646-650 Mauck, KF, Clarke BL. Diagnosis, Screening, Prevention, and Treatment of Osteoporosis. Mayo Clin Proc. 2006;81(5):662-672. Riggs BL, Melton LJ. The worldwide problem of osteoporosis: Insights afforded by epidemiology. Bone 1995;17:505S-511S.
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References: Lewiecki EM, Watts NB, McClung M. Position Statement: Official Positions of the International Society for Clinical Densitometry. J Clin Endo Metab. 2004;89(8):3651-55. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA 2002 288(15): 1889-97. Hodgson SF, Watts NB, Bilezikian JP. AACE Medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis. Endo Prac. 2003;9(6)545-564. Chapuy MC, Arlot ME, Delmas PD, Meunier PJ. Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 1994 308:1081-82.
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References: Recker RR, Hinders S, Davies KM et al. Correcting calcium nutritional deficiency prevents spine fractures in elderly women. J Bone Miner Res 1996 11:1961-66. Dawson- Hughes B Harris SS Krall EA et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age and older. NEJM 337:670-676. Liberman UA Weiss SR Broll I et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. NEJM 1995; 333:1437-1443. Black DM Cummings SR Karpf DB et al. Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. FIT research group. Lancet 1996; 348:1535-1541.
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References: Harris ST Watts NB Genant HK et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis:VERT study group. JAMA 1999, 282: 1344-1352. Reginster J Minne HW Sorensen OH et al. Randomized trial of the effects of risendronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporosis Int 2000, 11:83-91. Reginster JY Adami S Lakatos P et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 2006; 65:654-61.
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References: Ettinger B Black DM Mitlak BH et al. MORE Investigators. Reduction of vertebral fracture risk in postmenopausalwomen with osteoporosis treated with raloxifene. JAMA. 1999; 282:637-645. Chestnut CH Silverman S Andriano K et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: The PROOF study. Am J Med, 2000;109:267-76. Anderson GL, Limacher M Assaf AR, et al, Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.
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References: Cauley JA, Robbins J, Chen Z, et al, Women’s Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized controlled trial. JAMA 2003;290:1729-1738. The Medical Letter 3:38 2005. Rosen CJ Black DM Greenspan SL. Vignettes in Osteoporosis: A road map to successful therapeutics. J Bone Min Res. 2004;19: 3-15. Neer RM Armaud CD Zanchetta JR et al. Effect of parathyroid hormone on fractures and bone mineral density in postmenopausal women with osteoporosis. NEJM 2001;344:1434-1441.