Joop van den Bergh

ASBMR 2017: ten topics for clinicians

Netherlands:3 young investigator awards1 late breaking abstract

Fractures and fracture risk

[1086] Women Identified at High Risk of Hip Fracture based on

FRAX are Responsive to Appropriate Osteoporosis Management:

Results from the SCOOP Study of Population Screening

The recently completed primary-care based SCOOP screening study targeted treatment to those at highest hip fracture risk using FRAX.

Congress Highlights ASBMR 2017 Annual Meeting

• To examine the impact of the screening intervention on hip fracture risk according to baseline FRAX hip fracture probability

BACKGROUND

Fx: fracture; BMD bone mineral density

EUGENE MCCLOSKEY, CENTRE FOR METABOLIC BONE DISEASES, UNIVERSITY OF SHEFFIELD, UK

[1125] Longitudinal 5-year changes in bone density and

microarchitecture after Roux-En-Y Gastric Bypass

• RYGB leads to substantial postoperative bone loss, but it is unknown whether accelerated bone loss is sustained beyond 2 years.

• To evaluate longitudinal changes in BMD and bone microarchitecture in the 5 years after RYGB

BACKGROUND

• Prospective 5-year longitudinal study

• 21 adults (17F, 4M; mean age 51 ± 14 years)

• Severe obesity (BMI 45 ± 7 kg/m2), mean weight loss 33 kg, stable after 2 yearsSTUDY

• DXA lumbar spine, total hip, and 1/3 radius• QCT at L1-L2• HRpQCT to assess bone microarchitecture of the distal radius and tibia

ANALYSIS

RYGB: Roux-en-Y Gastric Bypass; DXA: dual X-ray absorptiometry; BMI: body mass index; QCT: quantitative computer tomography; L: lumbar; HR-pQCT: high resolution peripheral quantitative computer tomography

ELAINE YU, MASSACHUSETTS GENERAL HOSPITAL

[1055] Fracture Risk Among 122,205 Cancer Patients: A Population-Based Cohort Study from Manitoba, Canada

• Prior studies have assessed osteoporosis-related fracture risk among patients with breast or prostate cancer

• Data are limited on occurrence of fractures and their risk factors for other cancers

Congress Highlights ASBMR 2017 Annual Meeting

To estimate fracture risk for different cancers and determine predictors of fracture risk among cancer patients

BACKGROUND

• Identification of cancer cases and matched controls, covariates and fracture events through population-based administrative data from Manitoba Canada

• Case definitions for clinical vertebral, forearm, and humerus fractures (“major fractures” [MF])

• Fracture incidence rates and incidence rate ratios (IRRs)• Competing risk time-to-event analysis (competing event=death)

METHODS

MF: major fracture

WILLIAM LESLIE, UNIVERSITY OF MANITOBA, CANADA

[1055] Fracture Risk Among 122,205 Cancer Patients: A Population-Based Cohort Study from Manitoba, Canada

Congress Highlights ASBMR 2017 Annual Meeting

WILLIAM LESLIE, UNIVERSITY OF MANITOBA, CANADA

Fracture risk remains increased for up to 10 years after cancer diagnosis

compared to noncancer controls, similar for most cancer diagnoses.

Fracture risk factors in cancer patients are similar to traditional risk factors.

CONCLUSION

Relative risk of fracture: cancer patients versus controls and relationship to timing of

cancer diagnosis.

Dutch awardees

Screening for atypical femur fractures using extended femur scans by DXA

Denise van de Laarschot, Sandra Smits, Sanne Buitendijk, Merel Stegenga,

M. Carola Zillikens. Bone Center, Erasmus MC, Netherlands

• to evaluate the potential of extended femur scans by DXA as a screening tool forincomplete AFFs in all consecutive patients undergoing DXA

• who had used bisphosphonates or denosumab at any given moment in the previous year

• Beaking = a localized periosteal or endosteal thickening of the lateral cortex

Journal of Bone and Mineral Research, Vol. 32, No. 8, August 2017, pp 1632–1639

Young Investigator Award

Journal of Bone and Mineral Research, Vol. 32, No. 8, August 2017, pp 1632–1639

Journal of Bone and Mineral Research, Vol. 32, No. 8, August 2017, pp 1632–1639

• Beaking was detected in 12 out of 282 patients (4.3%)

• In 9 patients (3.2%) beaking corresponded with the radiological presence of incomplete AFFs

• 4 already had an X-ray made because of a previous complete AFF of the other leg

• 5 patients (1.8%) were newly diagnosed with six yet unknown incomplete AFFs

• The positive predictive value of beaking on extended femur scan was 83.3% in our study.

Journal of Bone and Mineral Research, Vol. 32, No. 8, August 2017, pp 1632–1639

Negligible Long-Term Effects on Bone Density after Four years of Treatment with TwoIntensive Combination Strategies, including initially High dose Prednisolone, in Early

Rheumatoid Arthritis patients: The COBRA-light Trial.

Merel JJ Lucassen, Marieke M ter Wee, Nicole PC Konijn, Debby den Uyl, Maarten Boers, Willem F Lems

• changes in bone mineral density (BMD) after four years in early RA patients initially randomized to one yearof COBRA or COBRA-light therapy

• (COBRA)-light therapy (methotrexate and initially 30mg/day prednisolone)

• non-inferior to

• COBRA therapy (methotrexate, sulfasalazine and initially 60mg/day prednisolone) in

• the first year of treatment of early rheumatoid arthritis (RA) patients

Young Investigator Award

4-year follow-up

COBRA-light COBRA

• Total Hip -3.3% (-1.7%) -1.7% (0.5%)

• Femoral Neck -3.7% (-1.0%) -3.0% (-0.6%)

• Lumbar spine -0.5% (-1.0%) -1.0% (0.0%)

Conclusion: in modern management of RA, one year of (initially high) glucocorticoid treatment has negligible long-term effects on bone.

High imminent vertebral fracture risk

in smokers and COPD patients with a

prevalent or incident vertebral fracture

Mayke van Dort Piet GeusensAnnemariek Driessen

Lisette RommeFrank Smeenk

Emiel WoutersJoop van den Bergh

The Netherlands

Young Investigator Award

Incidence of VFs

One year Three year0

20

40

60

80

100

None

1 VF

Subjects (%)with

incident VFs

HR 3.6*(2.9-4.6)

HR 5.4*(3.7-7.8)

VFs atbaseline:

Incidence of vertebral fractures within 1 and 3 years

*Cox proportional hazards, adjusted for age, sex, BMI, pack years, smoking status, having COPD

By baseline VF (y/n)

No

Yes

Incidence of VFs

One year Three year0

20

40

60

80

100

None

1 VF

Subjects (%)with

incident VFs

HR 3.6*(2.9-4.6)

HR 5.4*(3.7-7.8)

VFs atbaseline:

Incidence of VFs

One year Three year0

20

40

60

80

100

None

1 VF

**p for trend <0.001

Subjects (%)with

incident VFs

2 VF

**

**

VFs atbaseline:

By number of VFs at baseline

Incidence of vertebral fractures within 1 and 3 years

*Cox proportional hazards, adjusted for age, sex, BMI, pack years, smoking status, having COPD

By baseline VF (y/n)

**p for trend < 0.001

No

Yes

Incidence of VFs

One year Three year0

20

40

60

80

100

None

Grade 1

**p for trend <0.001

Subjects (%)with

incident VFs

Grade 2Grade 3

**

**

Severity atbaseline:

By severity of VFs at baseline

Incidence of vertebral fractures within 1 and 3 years

*Cox proportional hazards, adjusted for age, sex, BMI, pack years, smoking status, having COPD

**p for trend < 0.001

Incidence of VFs

One year Three year0

20

40

60

80

100

None

1 VF

Subjects (%)with

incident VFs

HR 3.6*(2.9-4.6)

HR 5.4*(3.7-7.8)

VFs atbaseline:

By baseline VF (y/n)

No

Yes

Mortality after a recent clinical fracture before and after the introduction of a Fracture Liaison Service

Caroline Wyers, PhD

ASBMR – September 11, 2017

Lisanne VrankenJohanna H Driessen

Irma JA de BruinPiet PM Geusens

Robert Y van der VeldeHeinrich MJ JanzingSjoerd Kaarsemaker

John A EismanJoop PW van den Bergh

LB-1160

HR*: 0.8095% CI: 0.72-0.90

Post

Pre

Mortality: Pre vs. Post FLS

* adjusted for age, sex and fracture type

Mortality – Fracture type

Minor fracture Major fracture Hip fracture

* adjusted for age and sex

HR*: 0.8195% CI: 0.67-0.98

Post

PreHR*: 0.8195% CI: 0.66-0.98

Post

Pre

HR*: 0.8095% CI: 0.75-0.98

Post

Pre

Behandeling

• Denosumab

• Abaloparatide

• Teriparatide

• Romosozumab

Effect of Denosumab Compared With Risedronate on Percentage Change in Lumbar SpineBMD at 12 Months in Subgroups of Glucocorticoid-treated Individuals

K Saag, N Pannacciulli, P Geusens,J Adachi, E Lespessailles, J Malouf-Serra, O Messina, A Wang, RB Wagman, WF Lems

Severe rebound-associated vertebral fractures afterdenosumab discontinuation

• These 9 cases are unusual and disturbing for several reasons

• All VFs were spontaneous and most patients had a high number of VFs(mean = 5.5) in a short period of time.

• Their VFs occurred rapidly after last denosumab injection (9 to 16 months)

Lamy et al. JCEM October 6, 2016

Denosumab behandeling gestopt en hervat:effect op BMD van wervel en heup

Behandeling

hervat met

60 mg Q6M

–2.4–1.8

Behandeling

gestopt

9.0

1.9

0 3 6 12 18 24 36 48–6

–2

0

2

4

6

8

10

12

14

–4

8.8

–1.3

*

*

–6

–4

–2

0

2

4

6

8

0 3 6 12 18 24 36 48

Behandeling

hervat met

60 mg Q6M

Behandeling

gestopt

–2.8–3.5

–1.2

3.9

5.0

–1.9

†

maanden maanden

Perc

enta

ge v

era

ndering

(gem

iddeld

e ±

SE

)

Wervel Heup

Placebo30 mg Q3M

*P = 0.004 op maand 36 en < 0.001 op maand 48 vs. placebo.

Miller PD et al. Bone (2008); 43(2), 222-229

Denosumab behandeling gestopt en hervat:effecten op botmarkers

–100

–80

–60

–40

–20

0

20

40

60

80

100

–100

80

100

Placebo30 mg Q3M

0 12 24 36 48 0 12 24 36 48Months Months

*

*

–80

–60

–40

–20

0

20

40

60

Serum CTx BSAP

*P < 0.001 op maand 36 en = 0.05 op maand 48 vs. placebo.†P = 0.01 vs. placebo.

Miller PD et al. Bone (2008); 43(2), 222-229

Behandeling

hervat met

60 mg Q6M

Behandeling

gestopt

Behandeling

hervat met

60 mg Q6M

Behandeling

gestopt

Perc

enta

ge v

era

ndering

(gem

iddeld

e ±

SE

)

Miller PD et al. Bone (2008); 43(2), 222-229

Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS

• Based on current data, denosumab should not be stopped without considering alternative treatment in order to prevent rapid BMD loss anda potential rebound in vertebral fracture risk.

• Re-evaluation after 5 years of denosumab treatment– high fracture risk should either continue denosumab therapy for up to 10 years

– or be switched to an alternative treatment

– low risk: bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover.

E. Tsourdi et al. / Bone 105 (2017) 11–17

LB abstract - Disco Dmab study

24 mnd

BP

Behandeling

• Denosumab

• Abaloparatide

• Teriparatide

• Romosozumab

JAMA. 2016;316:722-733

Behandeling

• Denosumab

• Abaloparatide

• Teriparatide

• Romosozumab

Lancet

Post-menopausal women > 45 years, T score <–1.50 At least two moderate or one severe prevalent vertebral fragility fracture

Behandeling

• Denosumab

• Abaloparatide

• Teriparatide

• Romosozumab

Original Article

Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis

Kenneth G. Saag, M.D., Jeffrey Petersen, M.D., Maria Luisa Brandi, M.D., Andrew C. Karaplis, M.D., Ph.D., Mattias Lorentzon, M.D., Ph.D., Thierry Thomas, M.D., Ph.D., Judy Maddox, D.O., Michelle Fan, Ph.D., Paul D. Meisner, Pharm.D., and Andreas

Grauer, M.D.

N Engl J MedVolume 377(15):1417-1427

October 12, 2017

Baron et al. Nature Medicine 2013: 179

Saag KG et al. N Engl J Med 2017;377:1417-1427

Effect van medicatie in de primaire analyses van RCTs met fractuurpreventie als eindpunt*

Medicament Wervel-fracturen Niet wervel-fracturen Heupfracturen

Follow-up Relatief effect Relatief effect Relatief effect

Alendronaat 1-4 jaar 0.55 (0.45-0.67) 0.84 (0.74-0.94) 0.61 (0.4-0.92)

Risedronaat 2-3 jaar 0.63 (0.51-0.77) 0.80 (0.72-0.90) 0.74 (0.59-0.94)

Zoledronaat 3 jaar 0.30 (0.24-0.38) 0.75 (0.64-0.87) 0.59 (0.42-0.83)

Denosumab 3 jaar 0.32 (0.26-0.41) 0.80 (0.67-0.95) 0.60 (0.37-0.96)

Teriparatide 1.5 jaar 0.36 (0.28-0.47) 0.62 (0.48-0.82)

Abaloparatide 1.5 jaar 0.14 (0.05-0.39) 0.57 (0.32-1.00)

Romosozumab (plac) 1 jaar 0.27 (0.16-0.47)0.75 (0.53-1.05)

0.58 (0.37-0.89)*

Romosozumab (Aln) 2 jaar 0.52 (0.40-0.66) 0.81 (0.66-0.99) 0.62 (0.42-0.92)

Teriparatide (Ris) 2 jaar 0.44 (0.29-0.68)

* Cave: rebound wervelfracturen na staken therapie