Muscle, Bone and Vitamin D: Are There Connections?

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Damon Jones
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University of Wisconsin School of Medicine and Public Health Madison, WI, USA Disclosures Research support Amgen GE Healthcare

1 Muscle, Bone and Vitamin D: Are There Connections? Endocrine Fellows Foundation, Sept 7, 2017 Neil Binkley, M.D. University of Wisconsin School of Medicine and Public Health Madison, WI, USA Disclosures Research support Amgen GE Healthcare Novartis Viking Consultant Amgen Radius Some of this talk is my opinion This is indicated by orange text Think, Don t Just Accept Dogma/Status Quo Only doubt is certain and disbelief worth believing. Without this courage there can be no learning. Believe nothing. Anonymous

$a consequent increase in bone fragility and susceptibility to fracture.$ $patients at risk for fractures will have their risk go unrecognized.$

2 Why Do You Treat Osteoporosis? Fracture is What s Important What is Osteoporosis? A systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis. Am J Med. 1991; 90:107- This is Not Osteoporosis if the clinical diagnosis is limited to a T-score diagnosis, a great many patients at risk for fractures will have their risk go unrecognized. Shouldn t an older individual determined to be at high risk be diagnosed as having osteoporosis? Siris, et. al, Osteoporos Int; 2012, 23:

$with hip fracture are being treated Kim, et. al., J Bone Min Res, 2016 DOI: 10.1002/jbmr.$

3 United HealthCare data; Proportion of patients in each quarter ( ) who received a BP or other osteoporosis med after hip fx n = 22,000+ Average age 72 68% female Less than 1 in 10 patients with hip fracture are being treated Kim, et. al., J Bone Min Res, 2016 DOI: /jbmr.2832 To draw an analogy from another field, in 2016 it is virtually inconceivable that a patient discharged from the hospital following a myocardial infarction would not be prescribed a full armamentarium of drugs for secondary cardiovascular prevention (eg, a statin, antihypertensive, and others). Yet what is inconceivable for a patient following a myocardial infarction is the norm in the vast majority of patients discharged from hospital after a hip fracture. Khosla and Shane, J Bone Min Res, 2016 DOI: /jbmr.2888 A Potential Approach to Improve the Osteoporosis Care Crisis Change the focus from osteoporosis to fracture Include ALL fractures in older adults Acknowledge that fractures affect QOL and independence Consider osteoporosis as just one part of a syndrome leading to fracture Need to address all components of the syndrome, not just the bones Binkley, et. al., J Bone Miner Res, :

4 Get Rid of the Fragility Fracture Concept Fragility Fracture, Osteoporosis-related Fracture, Lowtrauma Fracture, etc May Be Part of the Problem..we have demonstrated that there appeared to be nothing fragile about a fragility fracture based on patients communication of their fracture.. in other words, the term fragility or low trauma,...does not resonate with patients. Sale, et. al., Osteoporosis Int 2012, 23: Get Rid of the Fragility Fracture Concept Fragility Fracture, Osteoporosis-related Fracture, Lowtrauma Fracture, etc May Be Part of the Problem...even fractures occurring with intermediate or high trauma are predictive of recurrent fractures. As a result, we suggest that all fractures in older adults should be similarly evaluated for behaviors, risk factors and risk of recurrence that may benefit from interventions. Binkley, et. al., Submitted for publication 630 men and women over 8 years with a more than minimal trauma fracture More than minimal trauma defined as a force greater than minimal trauma but less than high trauma, e.g., MVA at > 30 km/h, falls from >4 m or significant physical assault Hand and foot fractures were included If age 50+, 55% had osteopenia and 23% osteoporosis.. We suggest that men and women over the age of 50 with a more-than-minimal trauma fracture should be investigated for low bone mass... Pereira, et. al., Osteoporos Int (2017) 28: DOI /s

Fractures = Need for Evaluation (Bone Attacks = Disease, Just Like Heart Attacks = Disease) I had a heart

$I broke my falling down the stairs. It was an accident; anyone would have fractured if they fell like I did.$ org/wod/2012 Need to Consider Osteoporosis as Part of a Syndrome Leading to Fracture; We Have Called this

org/wod/2012 Need to Consider Osteoporosis as Part of a Syndrome Leading to Fracture; We Have Called this

Name is Unimportant Rather than focusing on a single component, i.e., osteoporosis, sarcopenia, or obesity,

5 Fractures = Need for Evaluation (Bone Attacks = Disease, Just Like Heart Attacks = Disease) I had a heart attack climbing stairs. I have high cholesterol and blockages in the arteries to my heart. I broke my falling down the stairs. It was an accident; anyone would have fractured if they fell like I did. We Need to State that Fractures Reduce Quantity and Quality of Life Need to Consider Osteoporosis as Part of a Syndrome Leading to Fracture; We Have Called this Dysmobility (Difficulty Walking) but the Name is Unimportant Rather than focusing on a single component, i.e., osteoporosis, sarcopenia, or obesity, an opportunity exists to combine clinical factors thereby allowing improved identification of older adults at risk Such a combination could be termed dysmobility syndrome. Binkley, et. al, Osteoporos Int, 2013: 24:

$Focusing Only on Bone Identifies Less than Half of Women Who Will Fracture Only 44% of women (and 21% of men) who sustain non-vertebral fractures have osteoporosis by BMD 250 Number of non-vertebral$ $Our Guidelines Call this Osteoporosis The diagnosis of osteoporosis is established by measurement of BMD or by the occurrence of adulthood hip or vertebral fracture in the absence of major trauma$ $History of fall with scalp laceration 2 months prior Severe knee OA, unable to arise from chair without using his arms Slipped in his garage with left hip fracture at age 66; BMI = 34.$

6 Focusing Only on Bone Identifies Less than Half of Women Who Will Fracture Only 44% of women (and 21% of men) who sustain non-vertebral fractures have osteoporosis by BMD 250 Number of non-vertebral fractures participants in the Rotterdam study; Mean follow-up 6.8 yrs FN BMD at baseline (Female data shown here) Normal BMD Osteopenia Osteoporosis Adapted from Schuit, Bone. 2004;34: Despite the Fact That Approximately 1/6 Fragility Fractures Occur in People With NORMAL BMD. Our Guidelines Call this Osteoporosis The diagnosis of osteoporosis is established by measurement of BMD or by the occurrence of adulthood hip or vertebral fracture in the absence of major trauma (such as a motor vehicle accident or multiple story fall). NOF Clinician s Guide: 2014 Does This Man Have Osteoporosis? History of fall with scalp laceration 2 months prior Severe knee OA, unable to arise from chair without using his arms Slipped in his garage with left hip fracture at age 66; BMI = 34.9 We Need to Think About More Than Just the Bones and Focus on Fracture L1-L g/cm 2 T-score = +6.4 FN g/cm 2 ; T-score = +0.9 TF g/cm 2 ; T-score = Radius g/cm 2 T-score = +1.9

$Chronologic Age is a Poor Predictor of Functional Status There must be a better way to estimate a patient s fracture risk than simply using age.$

7 It is Clear That Low Bone Density, i.e., Osteoporosis is Only Part of the Clinical Constellation that Contributes to What is Currently Called Osteoporosis-Related Fracture Think Beyond the Bone Chronologic Age is a Poor Predictor of Functional Status There must be a better way to estimate a patient s fracture risk than simply using age. Why Do Fractures Increase With Age? Multiple reasons. Falls become common with advancing age ~1/3 rd of adults age 65 and >40% over age 75 fall each year Many osteoporosis-related fractures due to falls Over 90% of hip fractures due to falls Rizzoli, et. al, Curr Med Res Opin, 25: , 2009 Guideline for falls prevention; AGS/BGS, JAGS 49: , 2001

8 Does Age Truly Affect Fracture Risk? Dubbo osteoporosis study; 3851 men and women age 60+ All fractures x-ray confirmed Measured BMD, body sway and quad strength Subjects with fracture have significantly higher body sway and lower muscle strength than subjects without fracture and, more importantly, that age alone has NO influence on the probability of fracture. Nguyen, et. al., BMJ, 1993, 307: Falls Risk Factors Predict Hip Fracture Independent of BMD These risk factors include History of falls } Self reported health Indicators of Self reported physical activity Slower walking speed Impaired Function Sarcopenia/Impaired Function Is What Actually Predicts Fracture Masud & Morris. 2001, Age & Ageing 30;Suppl 4:3-7 Geusens et. al., 2010, Therap Advances Musculoskel Dis 2:63-67 Impaired Physical Performance Increases Hip Fracture Risk Evaluated the association of physical performance and hip fracture risk in MrOS; 5995 men age 65+ Poor physical function is independently associated with an increased risk of hip fracture in older men. Adapted from Cawthon, et. al., J Bone Miner Res, 2008, 23:

Sarcopenia: the Age-related Gradual Loss of Muscle mass, Strength and Function Sarc for flesh (muscle), penia for deficiency Term coined in 1989; more recently defined as: The ageassociated loss of

al, J Am Med Dir Assoc 2011; 12: 249-256 There is No Single Consensus Definition of Sarcopenia at This Time All current definitions include a measure of lean mass and measure(s) of physical function

9 Sarcopenia: the Age-related Gradual Loss of Muscle mass, Strength and Function Sarc for flesh (muscle), penia for deficiency Term coined in 1989; more recently defined as: The ageassociated loss of skeletal muscle mass and function. a complex syndrome associated with muscle mass loss alone or in conjunction with increased fat mass. Fielding, et. al, J Am Med Dir Assoc 2011; 12: There is No Single Consensus Definition of Sarcopenia at This Time All current definitions include a measure of lean mass and measure(s) of physical function Cruz-Jentoft, Age Aging, 2010, 39: Fielding, JAMDA, 2011, 12: Studenski, J Gerontol A Biol Sci Med Sci, 2014, 69: Osteoporosis Sarcopenia Pathogenesis is Multifactorial Hormonal declines GH/IGF-1, testosterone, estrogen Increased inflammation IL-6, TNF-alpha, etc, etc. Malnutrition Protein, vitamin D process? Sedentariness/Diseases leading to decreased use Toxin exposure Neuronal loss Reduced muscle bone quality expressed ultimately as reduced function Changes in structure, fat and connective tissue Are osteoporosis and sarcopenia the same With the disease being fracture? Jensen, J Parenter Enteral Nutr, 32; , 2008

$Women With Hip Fracture Often Have Sarcopenia and Osteoporosis by DXA 313 white women with low-trauma hip fracture Sarcopenia; ALM/Ht 2 < 5.45 kg/m 2 Osteoporosis; Femur T-score -2.5 We show.$

10 Women With Hip Fracture Often Have Sarcopenia and Osteoporosis by DXA 313 white women with low-trauma hip fracture Sarcopenia; ALM/Ht 2 < 5.45 kg/m 2 Osteoporosis; Femur T-score -2.5 We show.. A significant association between sarcopenia and osteoporosis in a large sample of hip-fracture women. Data supports preventive strategies and treatment options for sarcopenia and osteoporosis targeting both bone and muscle Adapted from Di Monaco, et. al, Arch Gerontol Geriatr, 52; 71-71, 2011 Interdependency of Bone and Muscle is Not a New Concept The mechanostat model of bone regulation was described in 1960 by Dr. Frost in his Utah Paradigm Holds that bone growth and loss is stimulated by local mechanical elastic deformation of bone due to muscle force. More muscle, more strain, more bone Less muscle, less strain, less bone Frost H.M., The Utah Paradigm of Skeletal Physiology Vols 1 and 2, ISMNI, 1960 Frost, HM. J Bone Miner Metab. 2000; 18: Frost, H Anat Rec, 2003: A 275A: Mechanics drive tissue formation and regulate tissue repair. Although the previous scientific decade has yielded a virtual flood of insight into how mechanics control tissue-specific gene expression in these biological processes, the basic mechanisms behind mechanobiological regulation remain unclear. Snedekar, J, BoneKEy Reports, 2014 Article #: 562 doi: /bonekey ,

$against fracture in postmenopausal women and is associated with increased risk of ankle and upper leg fractures. Compston, et al. Am J Med.$ 2011, 124:1043-1050 Too Little Bone, Too Little Muscle and Too Much Fat is Bad Should the Diagnosis be Osteo-Sarcobesity?

2011, 124:1043-1050 Too Little Bone, Too Little Muscle and Too Much Fat is Bad Should the Diagnosis be Osteo-Sarcobesity?

11 Even Bone + Muscle Isn t the Whole Story Obesity Increases Fracture Risk Global Longitudinal Study 60,393 women age 55 Followed for 2 years Our results demonstrate that obesity is not protective against fracture in postmenopausal women and is associated with increased risk of ankle and upper leg fractures. Compston, et al. Am J Med. 2011, 124: Too Little Bone, Too Little Muscle and Too Much Fat is Bad Should the Diagnosis be Osteo-Sarcobesity? Low Bone Mass Osteoporosis Low Muscle Mass Sarcopenia High Adipose Mass Obesity Dysmobility, i.e. Impaired Walking: This Also Allows Consideration of Other Things that Might Cause Difficulty in Walking or Increase Falls Risk, e.g., Balance, Neuropathy, etc, etc. Consider the Heart Attack Analogy Treatment is Directed at Various Conditions to Reduce Risk For a Potentially Catastrophic Outcome Metabolic Syndrome Advancing age Hyperlipidemia Hypertension Diabetes Obesity Family History Heart Attack Toxins, e.g., tobacco Reduced QOL Healthcare Cost Death

12 The Same Approach Makes Sense for Musculoskeletal Health, i.e., Bone Attack Treatment Should be Directed at Various Conditions to Reduce Risk For a Potentially Catastrophic Outcome Dysmobility Syndrome Advancing age Osteoporosis Sarcopenia Falls, Fractures Diabetes and Disability Obesity Family History Toxins, e.g., tobacco Reduced QOL Healthcare Cost Death NHANES data (n = 2975) assessed relationship between dysmobility and mortality in adults age 50+ Dysmobility was associated with increased mortality risk Additional work is needed to evaluate relationship with other outcomes Adapted from Looker A, Osteoporos Int 2015; 26: Dysmobility Syndrome Predicts Fractures Independent of FRAX Score 5,826 men in the MrOS cohort followed for a mean of 6.2 years ~7% had dysmobility defined as 3 of: Low BMD High fat mass Slow gait speed Low grip strength History of fall within past year Low ALM/ht 2 Dysmobility syndrome is an independent predictor of fracture, even when adjusted for FRAX score Buehring, et. al, presented at ASBMR 2016

Dysmobility Syndrome: An Important Concept but CLEARLY A WORK IN PROGRESS What factors to include requires further study: Arthritis? Multiple Fractures? Multiple and/or injurious falls Diabetes?

13 Dysmobility Syndrome: An Important Concept but CLEARLY A WORK IN PROGRESS What factors to include requires further study: Arthritis? Multiple Fractures? Multiple and/or injurious falls Diabetes? Neuropathy? Balance Etc, etc Factors likely need to have different weights rather than simply being scored equally Dysmobility syndrome (as crudely defined) predicts mortality and falls Additional studies need to examine whether it predicts other health outcomes, e.g., falls and fractures Diabetes Almost Certainly Should be Included as a Risk Factor Manitoba, CA clinical data 3518 M/W age 50+ with, and without DM at Time of BMD testing Mean f/u 5.4 years Fx ascertained by ICD code FRAX underestimated observed major osteoporotic and hip fracture risk in diabetics. We conclude that diabetes confers an increased risk of fracture that is independent of FRAX derived with BMD. Giangregorio, et al, J Bone Miner Res, 2012, 27: Integrating Dsymobility Risk into FRAX is an Ideal Way to Facilitate Clinical Implementation Falls Sarcopenia Diabetes Symptomatic Osteoarthritis One year probability of falls (%) Any fall Injurious fall 75 28

$If history of falls, particularly injurious falls and/or cannot arise without use of arms: Likely has dysmobility and is at increased risk for falls and fracture In Summary: THE HEALTH CONSEQUENCE OF$

14 We Do Not Require Calculators or Consensus: We Can Ask our Patients How many times have you fallen in the past year? Did any of these falls cause injury? Would you please stand up for me? If history of falls, particularly injurious falls and/or cannot arise without use of arms: Likely has dysmobility and is at increased risk for falls and fracture In Summary: THE HEALTH CONSEQUENCE OF IMPORTANCE IS FRACTURE Osteoporosis, Sarcopenia, Obesity, DM and Other Conditions are Part of the Fracture Risk Syndrome How Can We Take This to Clinical Care? Seems Likely That We Will Follow the Current Osteoporosis Paradigm Existing and Future Dysmobility Syndrome Treatments Look Like What We are Currently Calling Osteoporosis Treatment Nutrition Under-nutrition is common ~40% of hip fracture patients have energy/protein malnutrition Inadequate protein intake reduces muscle synthesis ~40% of older adults not meeting current RDA of 0.8 g/kg daily Protein intake of g/kg daily is likely optimal Calcium and Vitamin D Exercise/physical therapy/falls risk reduction Medications Hanger, et. al. N Z Med J ;112:88-90 Morley, J Nutr, Health, Aging, 12; , 2008 Mithal, et. al., Ost Int, 2013; doi /s y

Same as Drugs Meta-analyses of flawed studies yield flawed conclusions Most Studies Fail to Recognize That

15 The Bone Field Largely Has, and Continues, to Ignore Heaney s Guidance Heaney RP, Nutr Reviews 2013, 72:48-54 Robert Heaney, MD Virtually All Studies Fail to Recognize that Nutrients are Not the Same as Drugs Meta-analyses of flawed studies yield flawed conclusions Most Studies Fail to Recognize That We Are Not All The Same Binkley, et. al., currently unpublished Meta-analyses of flawed studies yield flawed conclusions

The IOM Recommends 1,000 mg of Calcium Daily Aged 19-50, 1200 mg Age 51+ And We Aren t Quite Getting There http://www.iom.

Calcium intake in the United States from dietary and supplemental sources across adult age groups: New estimate from the National Health and Nutrition Examination Survey 2003-2006, J Am Diet Assoc,

16 The IOM Recommends 1,000 mg of Calcium Daily Aged 19-50, 1200 mg Age 51+ And We Aren t Quite Getting There /Dietary-Reference-Intakes-for-Calcium-and- Vitamin- D/Vitamin%20D%20and%20Calcium%202010%20 Report%20Brief.pdf Manago KM et al. Calcium intake in the United States from dietary and supplemental sources across adult age groups: New estimate from the National Health and Nutrition Examination Survey , J Am Diet Assoc, 111: , The IOM Values are Consistent with Paleolithic Intake Paleolithic period > 2 million to ~10,000 years ago Humans began to cultivate plants and domesticate animals Hunter-gatherer diet consisted of: Animal source foods Lean meats, organs, bone marrow Uncultivated plants Fruits, nongrains, vegetables, nuts Paleo diet for this study included honey, eggs, pineapple, lettuce, celery, tomatoes, almonds, tuna, turkey, pork, chicken, oranges Average Paleo calcium intake 800 mg/day ± 400 mg/day Frassetto, et. al., Eur J Clin Nutr 2009: 63; NOF and ASPC convened an expert panel to evaluate the effects of dietary and supplemental calcium on CVD based on existing peer-reviewed literature The NOF and ASPC adopt the position that there is moderate-quality evidence (B level) that calcium with or without vitamin D intake from food or supplements has no relationship (beneficial or harmful) with the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults at this time. calcium intake from food and supplements that does not exceed the tolerable upper level of intake (2000 to 2500 mg/d) should be considered safe from a cardiovascular standpoint. Kopecky, et. al., Ann Int Med 2016:165:

Calcium Summary: Sept 2017 Aim for 1,000-1,200 mg/day Ideally through diet (+ supplements if needed) Close to the Paleo diet One serving is ~250 mg It is possible to get too much of anything; the

for Bone & Muscle USPSTF and AGS recommend vitamin D to reduce falls risk Common sense; target the level of highly sun exposed people Mean 25(OH)D 46 ng/ml Luxwolda, et. al.

17 Calcium Summary: Sept 2017 Aim for 1,000-1,200 mg/day Ideally through diet (+ supplements if needed) Close to the Paleo diet One serving is ~250 mg It is possible to get too much of anything; the jury is still out regarding vascular events There is no best calcium supplement Don t spend $$$$ If supplements are needed they should be taken with a meal Personal opinion Vitamin D Likely Important for Bone & Muscle USPSTF and AGS recommend vitamin D to reduce falls risk Common sense; target the level of highly sun exposed people Mean 25(OH)D 46 ng/ml Luxwolda, et. al., B J Nutr, V 108 / Issue 09 / November 2012, pp Be Aware that Assay Variability Persists: VDSP Guidance for 25(OH)D Assays, < 10% CV True value = 30 ng/ml (75 nmol/l) SD CV 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% SD 24.0 Acceptable With widespread adoption of VDSP proposed limits, a patients 25(OH)D result of 30 ng/ml is actually somewhere between ng/ml (60-90 nmol/l) 30 75

18 What to Do? Aim a Little High To Maintain Serum 25(OH)D of 20 ng/ml or 30 ng/ml Measured True Value Maintain Maximum 25(OH)D 20 ng/ml ~15 to ~ 25 ng/ml ~30 ng/ml 40 ng/ml 25(OH)D 30 ng/ml ~24 to ~36 ng/ml 40 ng/ml 50 ng/ml Recognize that the reported value may be low: with this approach, the maximum is likely to be ~40 to ~50 ng/ml, below that attainable by UV exposure Personal opinion Rarely Use 50,000 IU Doses of Vitamin D Human Physiology Expects Daily D 3 Input, Not Bolus Doses We don t really know what we are doing to vitamin D metabolism by providing huge, non-physiologic doses Heaney, et. al., Nutr Rev; 73(1):51 67, community dwelling women Age ,000 IU D 3 orally or placebo in fall or winter Falls and fractures 137 had 25(OH)D measured serially Median 25(OH)D ~50 ng/ml A temporal pattern of falls was observed with an increase only in the first 3 months annual oral administration of high-dose cholecalciferol results in an increased risk of falls and fractures. Sanders, et. al., JAMA, 303; , 2010

physiologic sense Ancestral human 25(OH)D mean is ~ 40 ng/ml Our current 25(OH)D measurements are imperfect Assay improvements are needed; progress being made RCTs with better study designs need to

19 Vitamin D Summary: Sept 2017 The field is in chaos (and passionate). Vitamin D inadequacy (however defined) is common Vitamin D is cheap and virtually side effect free Can t pick a single dose to assure whatever you believe to be vitamin D adequacy Daily dosing makes physiologic sense Ancestral human 25(OH)D mean is ~ 40 ng/ml Our current 25(OH)D measurements are imperfect Assay improvements are needed; progress being made RCTs with better study designs need to be conducted; This is not happening yet; expect chaos to continue Some Older Adults Have Phosphorus Deficiency And It Might Matter When Using Bone Drugs Phosphorus intake <70% of RDA in 10% of women age 60+; 15% age 80+ Low intakes also indicate low protein and calcium intake Potential for phosphorus deficiency increases if taking calcium supplements and bone active Rx Several courses of action present themselves at this stage of our ignorance. Most obvious is to use a calcium phosphate supplement. Heaney, RP in Nutrition and Bone Health, eds Holick & Nieves 2014; p 387 Protein Intake Recommendations: European Society for Clinical Nutrition and Metabolism Many reasons for higher protein needs Deutz,et. al., Clin Nutr, 33, , 2014

20 Expert Group Recommendations For health older people, the diet should provide at least 1.0 to 1.2 g protein/kg body weight/day Not clear whether best spread across meals or as a large pulse Not clear that specific amino acids, e.g., leucine, are best For older people who are malnourished or at risk of malnutrition (acute or chronic illness) diet should provide g/kg/day with even higher intake if severe illness Deutz,et. al., Clin Nutr, 33, , 2014 A protein intake of g/kg of body weight per day is probably optimal for older adults Mithal,et. al., Osteoporos Int, 24, , 2013 Muscle Medications Might Ideally be Used After Illnesses/Events to Get Back to Baseline Bone Active Medications Are Extremely Well Studied and Documented to Reliably Reduce Fracture Risk by ~50% In People at High Risk for Fracture, Especially Those Who Have Recently Sustained a Fragility Fracture, BPs (or other osteoporosis medications) Should be Prescribed for 3-5 years

Why Stop After 3-5 Years?? We have filled the remodeling space From Heaney, J Bone Miner Res 1994;10:1515 1523 And hyper mineralized the bone % of the total measurments 20.00 15.00 10.00 0.00 0.50.70.

21 Why Stop After 3-5 Years?? We have filled the remodeling space From Heaney, J Bone Miner Res 1994;10: And hyper mineralized the bone % of the total measurments Which might increase microcracks Over time, the changes in material-level properties could potentially override the structural-level benefits of bisphosphonates PLA ALN Boivin and Meunier, J Musculoskel Neuron Interact 2002; 2: Allen and Burr, BoneKEy-Osteovision 2007 February; 4(2):49-60 AFF Incidence Increases With Duration of Bisphosphonate Exposure 1.8 million Kaiser Permanente enrollees 45 years of age Potential AFF identified by ICD-9 diagnosis and CPT procedure codes All radiographs reviewed 142 femur fractures met ASBMR criteria for AFF 128 (90%) had previous BP exposure 14 (10%) no prior BP exposure Age adjusted incidence rose with increasing duration of BP exposure AFF Incidence Rate Age-adjusted per 100,000/year) BP exposure (years) ~ 1.1 per 1000 pt yrs after 10 years Adapted from Dell RM, J Bone Miner Res, 2012;27: Long-Term Treatment Risk/Benefit Numbers from ASBMR Task Force Per 100,000 patients Rx; Yr 9-10 NO data that hip or wrist fractures are prevented 1470 vert fx prevented 113 AFF caused (assuming; incorrectly) that ALL AFF are caused by BP 26 cases of ONJ caused 1470/139 = 10.6 spine fractures prevented per AFF/ONJ case caused Adapted from Adler, et. al., J Bone Miner Res, 2016; 31:16-35

$) After Hip Fracture Reduces Mortality and NH Readmission 124 patients with hip fracture 12 mo of high-intensity weight lifting exercise and targeted treatment of balance, osteoporosis, nutrition,$

22 Comprehensive Care (Dysmobility Syndrome Treatment?) After Hip Fracture Reduces Mortality and NH Readmission 124 patients with hip fracture 12 mo of high-intensity weight lifting exercise and targeted treatment of balance, osteoporosis, nutrition, vitamin D/calcium, depression, cognition, vision, home safety, polypharmacy and social support vs. usual care Note: Usual care included inpatient orthogeriatric and allied health consultation followed by 6-12 weeks of standard inpatient/outpatient physical therapy. Mortality NH Re-admit ADL decline was less and fewer use of assistive devices The intervention reduced mortality, nursing home admissions and ADL dependency compared with usual care. Adapted from Singh, et. al, JAMDA, 13: 24-30, 2012 Dysmobility Syndrome What To Do Today? Recognize fracture (not just osteoporosis) as the problem May be fatal May lead to inability to live independently Can be prevented (or at least have the risk for another fracture reduced) Reflects a syndrome, not just osteoporosis ALL fractures after age 50 require consideration of evaluation It s not just I fell Personal opinion Dysmobility Syndrome What To Do Today? Reduce falls Ask How many times have you fallen in the past year? Observe gait, ask to stand up without use of arms The usual falls risk reduction strategies including a PT consult Recognize that obesity may increase risk Optimize calories, calcium, vitamin D and protein status 2,000 IU daily is a reasonable place to start Measure 25(OH)D in those with falls/fractures Consider nutritionist evaluation Use existing osteoporosis medications to treat the bones Personal opinion

Fracture is the Outcome of Importance Due to a Syndrome

Factors We Need to Focus Not Just on Bone, But On the

physician treats the disease; the great physician treats

23 Fracture is the Outcome of Importance Due to a Syndrome of Osteoporosis, Sarcopenia, Obesity, Diabetes and Other Factors We Need to Focus Not Just on Bone, But On the Patient Treat the Person, Not Just Their Bones The good physician treats the disease; the great physician treats the patient who has the disease. Sir William Osler Thank You

Dysmobility Syndrome The Future of Fracture Risk Reduction

Dysmobility Syndrome The Future of Fracture Risk Reduction Canadian Musculoskeletal Conference, October 15, 2016 Neil Binkley, M.D. University of Wisconsin School of Medicine and Public Health Madison,