2Why Does it Matter? 44 million people in U.S. with low bone mass 2 million osteoporotic fractures per year$17 billion spent per year on osteoporotic fractures and their complications20% increased mortality over 5 years following a vertebral fracture10-30% increased mortality over one year following a hip fracture17% for women30% for men
3Why Does it Matter? 50% require nursing home care after hip fracture 30% need assistance with daily activitiesOnly 20% return to previous level of functioning
4DefinitionA microarchitectural deterioration of bone tissue resulting in decreased bone strength which predisposes to an increased risk of fractureBone strength = Bone density + Bone qualityBone mineral density (BMD) is usually used as a surrogate to assess bone strength
5Bone Mineral DensityFracture risk increases 2-3 times for each standard deviation below gender-matched young adult meanT score = #standard deviations from gender-matched young adult meanZ score = #standard deviations from age and gender-matched meanT score best correlates with fracture risk
6World Health Organization Definitions Normal – T score greater than or equal to -1.0Osteopenia – T score between -1.0 and -2.5Osteoporosis – T score less than or equal toEstablished osteoporosis – T score < -2.5 and at least one fragility fracture
7PathophysiologyBalance between bone resorption and formation (remodeling)Remodeling is in balance until about age 50Osteoclasts resorb boneOsteoblasts form boneEstrogen inhibits osteoclastic bone resorptionPeak bone mass is established by age 20 for the hip and during the early 30’s for the spine
8PathophysiologyWomen have increased incidence of osteoporosis compared to men due to:Lower peak bone massGreater bone loss after menopause (10% bone loss)Men and non-white women have higher peak bone mass than white womenGenetic factors – 70-80% of peak bone mass is genetically determinedPregnancy and lactation cause transient bone loss
9Pathophysiology Bone quality May be important in the future Disruption of microarchitectural elements of trabecular boneCortical thinningDecrease in degree of mineralizationMay be important in the future
10Types of Osteoporosis Primary osteoporosis Secondary osteoporosis Related to aging and/or decreased gonadal functionAging bone loss is slower than menopausalMenopause related bone loss lasts about 10 yrsSecondary osteoporosisDue to medications or chronic illnesses that accelerate bone lossConsider secondary osteoporosis if Z-score is low
13Case #170 year old female presents with a new vertebral compression fracture after slipping on the ice. She has never had BMD testing.PMHHTNHyperlipidemiaGERDDepression
14Case #1 MEDS Family hx – No hx osteoporosis known LisinoprilZocorProtonixCelexaFamily hx – No hx osteoporosis knownSocial hx – Non-smoker, no ETOH
15Case #1 Should her SSRI be stopped? Should her PPI be stopped? Should she have received BMD testing prior to starting these meds?
16SSRIs and Osteoporosis Canadian Multicenter Osteoporosis Trial – 2006Prospective cohort of 5008 adults 50 years old or greater, followed over 5 years for fractures137 were on SSRIsRisk of fragility fracture was increased 2 fold for pts on SSRIsRelative risk = 2.1 ( )Relative risk for corticosteroids =Study did not evaluate duration of SSRI use
17PPIs and Osteoporosis Prospective trial – (Roux 1/09) 1211 post-menopausal womenFor women on omeprazole the relative risk for vertebral fractures was 3.5 ( )Need more studiesFDA recommends considering shorter duration or lower dose of PPIPPI may interfere with calcium absorptionConsider calcium citrate supplementationNo studies on initial BMD testing prior to starting med
18Case #216 year old female presents for discussion of birth control options.PMH – NoneFamily hx – No hx osteoporosisSocial hx – No smoking, ETOH or drugsPt really wants Depo Provera but her Mom is concerned about side effects – she has heard that it weakens bones.
19DepoProvera Cross-sectional studies show decreased BMD in Depo users No studies have shown increased fracture risk with depo-usersBone mass increases with cessation of DepoFDA recommends stopping Depo after 2 years unless no other viable birth control optionsFDA suggests evaluating BMD for use greater than 2 years
20History – Risk FactorsHistory of fractures, esp. vertebra, hip or wristFamily history of osteoporosis or fragility fxs.Menstrual history – history of estrogen deficiencyNutritionExerciseHabits – tobacco, alcohol and caffeine use
21History and Physical Exam No reliable history or physical findings to identify patients with osteoporosisLook for risk factors and signs of occult vertebral fracturesLook for possible secondary causes of osteoporosisConsider further laboratory tests only if signs of a secondary cause
22History – Vertebral Fractures Back pain – acute or chronicLoss of height (>1 inch)Restrictive lung disease symptoms (exertional dyspnea, decreased exercise tolerance)Symptoms of reduced abdominal cavity (early satiety)Symptoms of depression, anxiety and fear
23Physical Exam Measure height and body weight Look for spinal tenderness and deformities (dowager’s hump)Look for tooth lossLook for protuberant abdomenSigns of secondary osteoporosisConsider home visit to assess risk for falling
24Risk Factors for Osteoporosis Non-modifiableFemale genderIncreased ageWhite or Asian raceFamily history of osteoporosisPersonal history of fracturePrevious hyperthyroidismRheumatoid arthritisSecondary osteoporosis
25Risk Factors for Osteoporosis ModifiableTobacco useSedentary lifestyleCaffeine use (tea is OK)Low calcium and vitamin D intakeAlcohol use (> 2 drinks per day)Hormone deficiency statesLow weight (BMI<21)Elevated homocysteine levelsCorticosteroid use (5 mg prednisone daily for 3 months)
26Risk Factors for Fractures History of fallingPoor physical conditionNeurological disordersImpaired vision and hearingCertain meds – sedatives, anti-hypertensivesEnvironmental hazards
27Environment Modification Remove throw rugsDecrease clutterHandrails on stairsImprove lighting, night lightsHandrails in tubs and showers, non-skid surfacesCane or walker if neededConsider hip protectorsWear supportive, low-heeled shoesTape down electric cords
28Case #3 63 year old female presents for a physical PMH Meds HTN GERD AnxietyMedsMetoprololOmeprazole
29Case #3 Social hx – smokes 1ppd, minimal ETOH Family hx – No osteoporosis or hip fracturesBMI = 23, Ht = 5-4Should she be screened for osteoporosis?
30Screening – Who to Screen? No studies showing decreased fracture risk with screeningHowever:Good evidence for increasing risk of osteoporosis and fracture with ageGood evidence that bone mineral density accurately predicts fracture risk (RR=2.6 for -1SD)Good evidence that treating asymptomatic women with osteoporosis decreases fracture risk
31Screening – Who to Screen? US Preventive Services Task Force recommendations based on current evidenceScreen all women > or equal to 65 yearsScreen women yrs. if at increased riskLower body wt. is best predictor of low BMDConsider using FRAXGrade B recommendations – fair to good evidence to support recommendation, benefits outweigh risks
32Screening – Who to Screen? USPSTF recommendations continuedNo recommendations for or against routine screening in women <60 yrs. or women yrs. with no increased riskScreening women at lower risk for osteoporosis can identify additional women who might benefit from treatment but would prevent smaller # fractures.Grade C recommendation – balance of benefits to harms is too close to make recommendation
33Screening – Who to Screen? USPSTF guidelines agree with guidelines of the National Osteoporosis Foundation and the American Association of Clinical EndocrinologistsAll recommend screening only if results will influence treatmentIf patient not in favor of treatment, DON’T SCREEN!
34Screening in Men National Osteoporosis Foundation Recommends screening all men over age 70 regardless of risk factorsEvaluate for risk factors and discuss calcium and vitamin D intake in all men >50Screen men ages with risk factorsHowever, very little evidence for or against screening men
35Screening Disadvantages CostPotential radiation exposurePotential unnecessary treatment for false positive or misinterpreted resultsIncreased anxiety and perceived vulnerability – can lead to increase in sedentary habits
36Risk Factor Assessment Which are best at predicting osteoporotic fractures?May help decide who to screen
37Risk Factor Assessment Age, weight and history of previous fracture correlate the best with low BMDFRAX = Fracture Risk Assessment toolDeveloped by WHO – 2008Estimates 10 year probability of major osteoporotic fractures and hip fracture
38Risk Factor Assessment FRAXAgeGenderPrior fractureLow BMIOral steroidsRheumatoid arthritisSecondary osteoporosisParental hx of hip fractureSmokingETOHPlus BMD
39Case #3 Decision is made to screen this patient Which test is the best test?
40Screening – Which Test?Conventional x-rays – osteopenia not detected until bone mass 40% decreasedBone turnover markers – experimental, expensive and no good evidence to support use (human osteocalcin, bone alkaline phosphatase)High false positive rate
41Screening – Which Test?All tests below have equivalent fracture risk predictabilityDual-energy x-ray absorptiometry (DEXA)Quantitative CTCalcaneal ultrasonography
42Screening – Which Test? Calcaneal ultrasonography Usually tests calcaneus onlyReflects other aspects of bone qualityMore portable testNo radiationLow costLow precisionDifficult to apply measurements to treatment protocols
43Screening – Which Test? Quantitative CT Usually tests spine and hip High radiationHigh costGood precision
44Screening – Which Test? DEXA Best validated test in studies and therefore considered gold standardResults vary by 6-15% when using machines from different manufacturersUsually test spine, hip or wrist (lateral spine)Low radiationIntermediate costExcellent precision – best if same machine is used and same technician
45Screening – Which Test? DEXA HOWEVER…… DEXA identifies fewer than half the people that go on to have an osteoporotic fracture
46Case #3 Her DEXA reveals a T-score = -1.5 When should she be retested if at all?
47Screening – How Often?Screening more often than every 2 years will not show accurate change in BMDRepeat screening more likely to be beneficial in older women and women with risk factorsNo evidence about follow-up BMD testing after initiation of treatmentNOF recommends follow-up BMD every 2 years on treatment
48Screening Summary Screen all high risk women Screen every 2 years Women < 65 with significant risk factorsMen with risk factorsScreen every 2 yearsConsider using risk assessment tools to determine high riskDEXA scan is best test (BUT not perfect)
49Case #3She gets repeat screening with DEXA in two years and the T-score is now -2.5Does she need evaluation for secondary causes of osteoporosis?
50Evaluating for Secondary Osteoporosis AACECBCCMPCa, Phos24 hour urine for Ca, Na, creatinine excretion25-hydroxyvitamin D levelAbove eval detects 90% of secondary osteoporosis
51Case #471 year old female presents for a review of her DEXA results which reveal a T-score of She has no hx of fractures and no family hx of fractures. She does not smoke. Her BMI=25.Do you tell her she has osteoporosis?Are her results normal?Do you recommend treatment for osteoporosis and if so what?
52Who to Treat?Definite reduction in fractures for treatment of BMD <-2.5 and for pts with history of fragility fracturesIs there any benefit in treating anyone else?
53What About Osteopenia? T score between -1.0 and -2.5 RCTs show no reduction in fracture risk for patients with T scores -1.6 to -2.5Individualize managementDecrease modifiable risk factorsIncrease calcium and vitamin D intakeIncrease exerciseDecrease tobacco, alcohol and caffeine use
54What About Osteopenia? Use FRAX calculator If assessed risk of hip fracture is >3% for the next ten years, consider treatmentIf risk of major osteoporotic fracture (wrist, vertebral, hip or proximal humerus) is >20% for the next ten years, consider treatmentUsing this calculator most pts with osteopenia will not be treatedNo actual studies on outcomes using FRAX
55Treatment Options Exercise Calcium and Vitamin D Estrogen BisphosphonatesRaloxifeneCalcitoninParathyroid hormone
56Case #565 year old, very healthy female has just found out she has osteoporosis. She does not want to “pollute her body with chemicals” and will only use “natural remedies”What do you recommend?
57ExerciseWeight-bearing activity – walking, running, aerobics, stair-climbing, strength training, dancing, court and field sportsNo data on cycling, skating or skiingExercise 3x/week for minutes durationStrength training reduces risk of falling alsoShort term exercise increases BMD by 2% in meta-analysis of 16 trials
58Exercise Cochrane review 2002 Meta-analysis 4/2004 (Kelley, et al) 18 RCTs of BMD in postmenopausal womenIncreased BMD of spine with any exerciseIncreased BMD of hip with walkingMeta-analysis 4/2004 (Kelley, et al)143 premenopausal womenResistance exercise did not increase or maintain BMD
59Calcium and Vitamin DRandomized controlled trials show improved BMD and decreased fractures with comboNNT = 48 to prevent one hip fracture after 1.5 years of treatmentNeed 1200 mg Ca/day and 800 IU vit. D/dayCalcium better absorbed if taken with food and 600 mg or less at a timeCost = $5/month
60Calcium and Vitamin DCalcium citrate is slightly better absorbed than Ca carbonateConsider using Ca citrate if patient on acid blocker medCa carbonate – Oscal, Caltrate, Tums, ViactivCa citrate - Citracal
61Calcium and Vitamin DSide effects of calcium include dyspepsia, gas, bloating and constipation(10%)May interfere with absorption of tetracycline or quinolonesIf history of kidney stones evaluate for hypercalciuria prior to giving calciumRecent meta-analysis based on WHI showed slight increase in MI and stroke in pts taking Ca with or without vitamin D (Bolland 4/11)RR of MI = 1.24 ( )
62Calcium Cochrane review – 2004 15 RCTs, 1806 subjects Small improvement in bone density after 2-3 yrsTrend toward decrease in vertebral fracturesUnclear if calcium alone decreases non-vertebral fractures
63Vitamin D Vitamin D deficiency Decreased calcium absorption PTH-mediated increase in bone resorptionDecreased muscle strength and increased falls
64Vitamin D Cochrane review – April 2009 Vitamin D alone showed no sig. effect on hip or vertebral fracture rateVitamin D with calcium slightly reduced non-vertebral fractures, but no effect on vertebral fracturesNo evidence that analogs of vitamin D offer any advantage over native vitamin DVitamin D2 and vitamin D3 equally effective
65Vitamin D National Osteoporosis Foundation Recommends 800 – IU dailyConsider testing in pts at risk for deficiencyElderlyMalabsorption diseasesChronic kidney diseaseHousebound patientsTest serum 25(OH)D level should be between (toxicity > 100)
66Folate and Vitamin B12 RCT (Sato – 3/2005) 628 pts, s/p stroke 5 mg folate and 1500 mcg of B12 vs placeboDecreased hip fractures in treated groupNNT = 14
67Magnesium Often taken by patients No studies show decrease in fracture rate or increase in BMD
68PhytoestrogensAct as weak estrogens but also have anti-estrogen effectsPrimary source of phytoestrogens is isoflavones which are found in soybeans(less in tofu) and lignans (flaxseed; some cereals, fruit, vegetables, and legumes)Secondary sources are black cohosh and red clover
69PhytoestrogensSmall studies show some decrease in hot flushes and vaginal drynessNo human studies showing effect on boneDosage, purity, and adverse effects unknownEstreven and Remifemin are combinations of isoflavones, black cohosh and red clover
70Estrogen Replacement Therapy WHI (Women’s Health Initiative Study)NNT = 2000 to prevent one hip fracture after 5 years of treatmentNot as effective for treatment but has definite benefit for preventionStrongest benefit for ERT is for women < 60HERS showed no sig. decrease in fracture rate over 4 yearsFDA approved only for prevention
71ERT Transdermal and oral forms equally effective MUST use progesterone with estrogen if patient has intact uterusEstrogen with or without progesterone is equally as effectiveCost = $14-28/monthSecondary benefit of decreasing menopausal symptoms
72ERT - HarmsWHI studySmall increased risk of 22% for cardiovascular events (7 additional cases/10,000/yr)26% increased risk of invasive breast cancer (8 additional cases/10,000/yr)41% increased risk of stroke (8 additional cases/10,000/yr)2-fold increased risk of pulmonary embolismSE’s – Vag. Bleeding, nausea, headache, mood alterations, breast tenderness, bloating
73Bisphosphonates Work by inhibiting osteoclastic activity RCT’s show significant and rapid reduction in fracture risk for women with previous fracture and osteoporosisEvidence not as good for women without previous fracture
74Alendronate (Fosamax) NNT = 34 to prevent one vert. fx over 3 yrs.NNT = 86 to prevent one hip fx over 3 yrs.Dose = 5-10 mg/day or mg/weekForms – oral solution, Fosamax with D weeklyCost = $95/monthSE’s – nausea, dyspepsia, esophageal ulcer, esophagitisWeekly dosing showed equivalent increase in BMD to daily dosing (no data on fractures)
75Alendronate Meta-analysis of RCTs – (Papapoulos – 5/05) Post-menopausal womenDose = 5-10 mg/day for yrsOverall risk reduction for hip fractures of 55% in pts with osteoporosisClinically sig decrease in hip fractures
76Risedronate (Actonel) NNT = 15 to prevent one vert. fx over 3 yrs.NNT = 91 to prevent one hip fx over 3 yrs.Dose = 5 mg/day, 35 mg/week, 150 mg/monthCost = $150/monthSE’s – abdominal pain, nausea, diarrhea but not sig. different from placeboNo sig. GI adverse events even in patients with history of ulcers, GERD, or taking NSAIDS
77Risedronate Cochrane systematic review – 8/2003 8 RCTs Postmenopausal women received 5 mg/day, compared to Ca or placeboIncreased BMD after 3 yrsDecreased vertebral and non-vertebral fracturesNo difference in side effects compared to placebo
78Ibandronate (Boniva) BONE study – (Delmas – 9/2003) Large multi-national RCTOral Ibandronate Osteoporosis Vertebral Fracture Trial in N. America and Europe2946 post-menopausal womenDaily or intermittent ibandronate vs placeboDecreased risk for vertebral fractures by 50-62%NO decreased risk of non-vertebral fractures
79Zoledronic Acid (Reclast) Given IV every 12 monthsDecreases both vertebral and hip fracturesExpensiveConsider only in certain high risk pts
80Bisphosphonates Less than 1% of each dose is absorbed Optimize absorption by taking with full glass of water and 30 mins prior to breakfastAvoid GI problems by standing or sitting for 30 mins after taking medDo not use in patients with creatinine clearance <30 ml/min or hypocalcemiaAccumulates in bone – long term effects unknown
81Bisphosphonates Does one work better than another? Head to head RCT of alendronate 70 mg/week and risedronate 35 mg/week (Rosen-1/2005)Total of 1053 postmenopausal women with osteoporosis, studied over 12 monthsAlendronate showed greater increase in BMD compared to risedronateFracture rate not assessedBoth drugs tolerated equally well
82Case #6 72 year old female with T-score = -2.7 and no hx fracture. You have recommended starting a bisphosphonate but she has heard that these drugs cause cancer and a jaw problem.What do you say?
83Bisphosphonates Osteonecrosis of the jaw (ONJ) Canadian Consensus Practice Guidelines (6/2008)ONJ has been clearly associated with use of high dose IV bisphosphonates in the treatment of cancerONJ has NOT been clearly linked with low-dose bisphosphonates used for osteoporosisAdvise good oral hygiene and regular dental visitsConsider holding drug for non-emergent dental surgery
84Bisphosphonates Atrial fibrillation Systematic review – (Loke – 2009) Results of studies were mixedThere may be a link with bisphosphonates and atrial fib but data was too heterogeneous to make a determinationNo increase in stroke risk or cardiovascular mortalityFDA fells this is a chance finding
85Bisphosphonates Subtrochanteric fracture Esophageal cancer Occur after minimal or no traumaDirect etiologic relationship not yet substantiatedEsophageal cancerIncidence went from 1 case per 1000 in untreated pts to 2 cases per 1000 in those treated with bisphosphonates for 5 years or moreConsider drug holiday of 1-2 years after 3-5 years of therapy
86Case #775 year old female with hx osteoporotic vertebral fx cannot tolerate the bisphosphonates. She has hx of severe GERD and peptic ulcer disease.What do you recommend?
87Selective Estrogen Receptor Modulators Raloxifene (Evista)Blocks action of cytokines which stimulate bone resorptionRCT’s show sig. decrease in new vertebral fractures for women with previous history of fracture and osteoporosisNNT = 29 to prevent one vert. fx over 3 yrs.NO evidence of decrease in hip fractures
88Raloxifene Dose = 60 mg/day Cost = $150/month Secondary benefit may be reduction of breast cancer riskSE’s – leg cramps(3%), hot flashes(6%), risk of venous thromboembolism (1 in 465 women/yr)Does not increase risk of endometrial hyperplasia or cancer
89Salmon Calcitonin Calcitonin nasal spray (Miacalcin) Large RCT showed decreased new vertebral fractures in women with previous history of osteoporotic vertebral fx.No effect reported for hip fracturesNo definite effect for women with no previous osteoporotic fx.Increased BMD less than that seen with bisphosphonates or estrogen
90Salmon Calcitonin Dose = 200 IU/day, 1 spray in 1 nostril qd Cost = $112/monthSE’s – rhinitis(5%), epistaxis, sinusitisAlternate nostrils to decrease SE’sSecondary benefit of decreased pain from vertebral fractures
91Parathyroid Hormone Stimulates bone formation Teriparatide (Forteo) – recombinant PTHRCT shows 1/3 decreased incidence of vert. fx and ½ decreased incidence of non-vert. fxDose = 20 mcg SC qdLess convenientMore expensive - $1000/monthSEs – nausea, headache, hypercalcemia, dizziness, leg cramps, ? risk osteosarcomaMeasure Ca, vitamin D and PTH levels prior to treatment
92Parathyroid Hormone FDA black box warning Teriparatide caused osteosarcoma in rats using much higher doses of the drugDrug is contraindicated in pts at risk for osteosarcomaPagets disease of boneHx of irradiation involving the skeletonUnexplained elevation of alkaline phosphataseSafety after 2 years duration is unknown
93Parathyroid Hormone RCT – (Neer – 5/01) 1637 post-menopausal women with prior vertebral fracturesAverage T-score = -2.620 or 40 mcg PTH vs placeboNNT = 11 to prevent one vertebral fracture40 mcg dose worked a little better but had more side effects (hypercalcemia)
94Parathyroid Hormone RCT – (Body–10/02) 14 months duration Compared PTH to alendronatePTH increased BMD in hip and spine more than alendronate (12.2% vs 5.6%)Non-vertebral fracture rate was lower in the PTH group
95Denosumab Monoclonal antibody against RANKL Decreases osteoclastic activityBrand name – Prolia60 mg SQ every 6 monthsStudies show reduced fractures of the hip, spine and non-vertebral sitesSEs – Skin infections, dermatitis, ? osteonecrosis of the jaw
96Combination TherapyNo studies demonstrating reduction in fracture riskMore improvement in BMD with combined estrogen and alendronateRCT of combined PTH and alendronate showed no improvement over PTH alone (Finkelstein-2003)AACE does not recommend combined therapy
97Treatment Monitoring AACE guidelines DEXA every 1-2 years until stable BMD should be stable or increasing and there should be no fracturesIf this is not the case consider different treatment
98Osteoporosis in Men 30% of hip fractures occur in males 1.5 million men >65 have osteoporosisMay have higher mortality rate compared to females2/3 have secondary osteoporosisHypogonadism, glucocorticoid use, etc.Risk increases with age but later than in women
99Osteoporosis in Men Treatment 1000 mg/day calcium and 800 IU/day vitamin DExerciseIf hypogonadism, consider testosteroneBisphosphonates – RCT of alendronate 10 mg/day showed sig increase in BMD and decrease in vertebral fractures (Orwoll – 8/2000)PTH – RCT of PTH 20mcg/day showed increased BMD (Orwoll – 1/2003)
100Prevention SummaryStart adequate calcium and vitamin D intake in childhoodEncourage exerciseDecrease risk factors for osteoporosisDecrease risk factors for fallingConsider bisphosphonate for prevention if high risk
101Treatment Summary AACE recommendations 1st line – alendronate, risedronate, zoledronic acid, denosumab2nd line – ibandronate, raloxifeneLast line – calcitoninTeriparatide only for pts that fail aboveNo combination therapy
102ReferencesPrevention and Treatment of Osteoporosis in Postmenopausal Women. JFP October 2002Screening for Osteoporosis in Postmenopausal Women: Recommendations and Rationale, US Preventive Services Task Force. Ann. Intern. Med. 17 Sept. 2002Radiologic Bone Assessment in the Eval. of Osteoporosis. AFP April 2002Cauley, JA. Effects of HRT on clinical fractures and ht loss(HERS). Am J MedPapapoulos, SE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporosis Int May.Delmas, PD. Daily and intermittent oral ibandronate normalize bone turnover and reduce vertebral fracture risk: results from the BONE study. Osteoporosis Int April.
103ReferencesCalcium Supplements. The Medical Letter April 3, 2000Osteoporosis: Parts I and II AFP March 2001Cochrane DatabasePetitti, DB. The WHO Study of Hormonal Contraception and Bone Health. Ob-Gyn May.Orr-Walker, BJ. The effect of past use of the injectable contraceptive depot medroxyprog. acetate on bone mineral density in normal post-menopausal women. Clin Endocrinol Nov.Kelley, GA. Efficacy of resistance exercise on lumbar spine and femoral neck BMD in premenopausal women: a meta-analysis. J Womens Health April.Sato, Y. Effect of folate and mecobalamin on hip fractures in pts with stroke: a RCT. JAMA March.
104ReferencesBauer, DC. Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Arch Intern Med Jan.Neer, RM. Effect of PTH on fractures and BMD in postmenopausal women with osteoporosis. N Engl J Med MayBody, JJ. A randomized double-blind trial to compare the efficacy of teriparatide with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab Oct.Orwoll, E. Alendronate for the treatment of osteoporosis in men. N Engl J Med Aug.Orwoll, ES. The effect of teriparatide therapy in men with osteoporosis. J Bone Miner Res Jan.AACE Guidelines for Diag and Treatment of Osteoporosis