SBMR 2019 highlights, vanuit de endocrinologie

1. ASBMR 2019
highlights
Joop van den Bergh

2. Topics
• Epidemiology
• FLS care
• Imaging
• Various topics

3. Time Since Prior Fracture is Associated with Subsequent Fracture Risk:
An Analysis of Real-World Data (Sweden)
1158

4. Subsequent Fracture Risk
Following Traumatic versus Non-traumatic Fracture
• Study population: 80.242 individuals (mean age 64±11) years
• 858 with prior traumatic and 14,758 with prior non-traumatic fractures
• During median follow up of 9 years
• Baseline BMD Z-scores (femur neck, total hip, lumbar spine) were similar for those with prior
traumatic and non-traumatic fractures regardless of fracture site
• Both were lower than in those without prior fracture
Leslie et al. 1154

5. 1154

6. Grade 1 vertebral fractures identified by VFA predict incident fracture
independently of clinical risk factors and BMD in older women
• Population-based study of 3,028 women (Gothenburg area, Sweden)
• 75-80 years of age at baseline
• 3.6 years follow-up
• Genant VF classification
Lorentzon 1155

7. Grade 1 vertebral fractures identified by VFA predict incident fracture
independently of clinical risk factors and BMD in older women
1155

8. Site-specific prediction of fractures by BMD and bone microarchitecture in older
women and men: The Bone Microarchitecture International Consortium (BoMIC)
Biver et al. 1156

9. Men 80-89 Years with Osteopenic BMD have Substantial 5-year Risk of Hip Fracture
Accounting for Competing Mortality and Chronic Conditions
Orwoll et al. LB SAT-1051

10. Men 80-89 Years with Osteopenic BMD have Substantial 5-year Risk of Hip Fracture
Accounting for Competing Mortality and Chronic Conditions
Orwoll et al. LB SAT-1051

11. Men 80-89 Years with Osteopenic BMD have Substantial 5-year Risk of Hip Fracture
Accounting for Competing Mortality and Chronic Conditions
Orwoll et al. LB SAT-1051

12. Racial Disparities Exist in one year Outcomes Post Major Fragility Fractures
(xx/1000 patient years)
Saag et al. 1125In women with osteoporosis

13. The association of bone turnover during the menopause
transition and subsequent fracture:
• urine N-telopeptide (U-NTX – bone resorption) and fracture data from 484
participants in the longitudinal Study of Women’s Health Across the Nation
(SWAN).
• MT: 2 years before to 2 years after the final menstrual period (FMP)
• After MT was defined as after 2 years following the FMP
Cauley et al. 1124

14. The association of bone turnover during the menopause
transition and subsequent fracture:

15. Loss in DXA-Estimated Total Body Lean Mass but not Fat Mass Predicts Incident
Major Osteoporotic Fracture and Hip Fracture
Leslie et al. 1061total body lean mass (TBLM) and total body fat mass (TBFM) estimated from DXA
DXA median interval 3.3 years, follow-up 6 years, HR per SD loss

16. Increases in Visceral Adipose Tissue Over Six Years Result in Lower Paraspinal Muscle Density in
Men and Women: the Framingham Study
Since lower paraspinal muscle
tissue density has been
associated with increases in
postural sway and falls, VAT
may represent a modifiable
risk factor for poor
musculoskeletal outcomes
with aging.
Bouxsein 1062

17. The Risk of Hip and Non-Vertebral Fractures in Chronic Kidney Disease:
A Systematic Review and Meta-Analysis
Cummings 1071
1
2

18. Type 2 Diabetes Mellitus and the risk of osteoporotic vertebral fractures:
a meta-analysis
Diabetes Care 2019 online Fr 633

19. A Novel Fracture Prediction Model Using Machine Learning in
Community-Based Cohort Study
• 3 different machine learning models, CatBoost, support vector machine (SVM) and a logistic
regression model
• Compared with FRAX® scores by area under the curve (AUC)
• 7.5-year follow-up (range 2.5–10 years), fragility fractures occurred in 537 (25.6%) of participants
• In predicting total fragility fractures, AUC values of the CatBoost, SVM and logistic regression
models were 0.688, 0.500 and 0.614, respectively.
• The AUC value of Cat-Boost was significantly better than that of FRAX® (0.663, p<0.001) while
SVM and logistic regression model were not.
• Compared to the conventional models such as SVM and logistic regression models, the CatBoost
model had the best performance in predicting total fragility fractures (p<0.001). According to
feature importance in the CatBoost model, top predicting factors listed in order were total hip,
lumbar spine, and femur neck BMD, subjective arthralgia score, serum creatinine, and
homocysteine. The latter 3 factors were listed higher than conventional predictors such as age or
previous fracture history
1117

20. 1117

22. Topics
• Epidemiology
• FLS care
• Imaging
• Various topics

23. The imminent subsequent fracture risk in patients with a recent fracture at the FLS
is mainly associated with falls – a 3 year prospective cohort study
• 60% sustained a fall, 60% were recurrent fallers
• Fall risk highest in first year
• 11% with at least one subsequent FX during 3 years
• 16.2% in fallers, 2.1% in non fallers
• Risk in treated patients 2x the risk of untreated patients
• 90% of index fracture and 85% of subsequent fractures directly caused by a fall
LB SAT-1052

24. Effect of denosumab on falls, muscle strength and function in
community dwelling older adults
• FREEDOM Study: significant reduction in falls in the Dmab group, although mechanisms explaining this effect
remain unknown.
• 79 community-dwelling older adults (≥65 years) presenting with a high risk of falls and/or fractures from
western Melbourne, Australia participated in this study.
• Participants were prescribed either Dmab (N=51) or zoledronic acid (ZOL) (N=28) with a 6-month follow-up
where assessments were repeated.
• Median age: 80 years in Dmab and 77.5 in ZOL.
• At the 6-month follow up, the Dmab group
• improved gait speed by 0.06m/s (0,0.1 p=0.041)
• Time to complete the TUG
• Fear of falling declined (p=0.01)
• Balance improved by 7.8%
• Conclusion: Dmab displayed a positive effect in improving balance, function and fear of falling, which may
explain its anti-fall efficacy.
Kirk. LB-1170

25. Home visits in FLS non-responders

26. Fracture liaison services: do they reduce
fracture rates?
De Bruin et al. Ther Adv Musculoskel Dis 2017:157

27. FLS Implementation was associated with reduced risk of recurrent
clinical fractures in patients with osteoporotic fracture
• 15.968 patients (73.5±12.4yrs), 76% women
• major osteoporotic index fracture (hip, clinical spine, humerus, radius and pelvis)
• FLS period (n=10,898) compared to period prior to FLS implementation (n=5070)
• Intention to treat analysis
• Median follow-up time of 2.1 years
• The use of osteoporosis medication within the first year of index fracture
increased from 14% to 27% after FLS implementation.
• The rate of recurrent fracture per 1000 patient-years was 32.5 in the control
period and 29.6 in the FLS period.
• Hazard Ratio 0.79 (95% CI 0.70- 0.89), p<0.001, corresponding to a 3-year number
needed to screen (NNS) of 50
Axelsson 1126

28. FLS Implementation was associated with reduced risk of
recurrent clinical fractures in patients with osteoporotic fracture
1126

29. Topics
• Epidemiology
• FLS care
• Imaging
• Various topics

30. Longitudinal Development of Peak Bone Mass in White U.S. Females
Whole body bone mineral content (WBBMC, g) was measured annually, contemporaneous with stature, in 3 prospective longitudinal cohorts
peak bone mass by chronological
age 21 yrs, 10 yrs post-menarche
Cole 1016

31. Surrogate threshold effect: a novel approach for potential approval
of new osteoporosis treatments using 24-month change in TH BMD
Eastell 1090JBMR 2019: 632

32. Eastell 1090

33. Trials sorted by 2-year difference in TH BMD
Fracture reduction:
Not significant
Not available
P<0.05
P<0.01
Note: difference in placebo group is often
reported to be between NA or between 0
and -1.0 to -2.0%
Eastell 1090

34. Bone Quality and Long-Term Bisphosphonate Use in
Women with Osteoporosis
• FEA-bone strength increased with BP treatment duration, peaked at ~7.3 years, then declined
Pienkowski 1088
iliac crest bone samples
uCT
nanoindentation

35. Microcrack density increased with BP treatment duration and microcrack length trended upward
1088

36. Extensive Modeling-Based Bone Formation After 2 Months of
Romosozumab Treatment: Results From the FRAME Clinical Trial
Eriksen 1049

37. 1049
Stimulation of bone formation in the first 2 months of Romo treatment is predominately due to
increased Modeling Based Bone Formation on the endocortical and cancellous surfaces.

38. • Postmenopausal women wit osteoporosis and vertebral or hipfracture
• 2 groups: Romo 210 mg sc/month or ALN 70 mg/week for 12 months, followed by open label ALN
• Substudy: BMD Lumbar spine with QCT (n=76) and FEA (n=86) on baseline, 6,12 en 24 maanden
Romosozumab Improves Lumbar Spine Bone Mineral Density and Bone Strength
Greater Than Alendronate as Assessed by Quantitative Computed Tomography and
Finite Element Analysis in the ARCH Trial
Brown 1050

39. Romosozumab Improves Lumbar Spine Bone Mineral Density and Bone
Strength Greater Than Alendronate
1050Higher vBMD and FEA Bone strength at 6, 12 and 24 months

40. 18F-NaF PET/CT in Forty-four Patients with Fibrodysplasia Ossificans Progressiva
Uncovers Highly-prevalent, Multifocal, Metabolically-Active Heterotopic
Ossification, Largely Disassociated from Flare-ups
70% of patients showed two or more active lesions, only 3
of 41patients demonstrated flare-up within 7 days of the
baseline
Botman 1038

41. Topics
• Epidemiology
• FLS care
• Imaging
• Various topics

42. Hypercalcemia after cosmetic paraffin oil injections
Jensen 1020

43. Hypercalcemia after cosmetic paraffin oil injections
• All men – even those with normocalcemia – had high urinary calcium
excretion
• nephrolithiasis from 21% in normocalcemic patients with normal PTH,
to 54% in hypercalcemic men
• 1,25(OH)2D3 was significantly higher
• Enzyme activiation -> production of 1,25(OH)2D3

44. Involvement of the gut microbiota and barrier function
in glucocorticoid induced osteoporosis
• GCs directly induce osteoblast and osteocyte apoptosis but can affect other organs including the
intestine
• Examination of stool from healthy and GC treated mice demonstrated that GC treatment alters
the gut microbiota composition
• Broad-spectrum antibiotic treatment to deplete the microbiota: prevented GIOP (-40%)
• Probiotic (Lactobacillus reuteri) treatment also prevented GIOP
• GC treatment causes intestinal barrier leaks and increases serum endotoxin levels -> target for
preventing GIOP
Schepper 1123

45. Intravital imaging of osteoclasts in vivo reveals novel osteoclast fate which may
underlie the therapeutic response to Denosumab withdrawal
• Osteoclast dynamics on the intact endocortical surface of tibia in live mice
• Following stimulation with sRANKL we visualized osteoclast fusion and for the first time osteoclast
fission in vivo, which was shown to be morphologically distinct to apoptosis.
• Interestingly we observed osteoclast fission products re-fusing with parent cells or other
osteoclasts, a process we termed osteoclast recycling.
• Critically, 3-4 weeks following OPG-Fc withdrawal, recycling osteoclasts had re-fused to form
active osteoclasts, resembling stimulation with sRANKL.
• This increase in osteoclasts with resulted in increased serum TRAP and subsequent loss in bone
microarchitecture.
Biro 1129

46. Calcif Tissue Int (2012) 90:515–522

47. Calcif Tissue Int (2012) 90:515–522

48. Fission of osteoclast
Calcif Tissue Int (2012) 90:515–522

49. Fracture Risk in Trans Women and Trans Men Using Long-Term
Gender-Affirming Hormonal Treatment
Wiepjes / den Heijer