To enhance state-of-the-art knowledge and expert care for osteoporosis and other metabolic bone disorders in Lebanon through education, research and service.

To join OSTEOS please visit our website on: http://www.osteos.org.lb For your suggestions, please contact us: osteos@osteos.org.lb

Welcome note

Dear colleagues,

Despite the sad events and losses of innocent blood that happened at the end of 2013 and the beginning of 2014, we can say that 2013 was a “Bone” Année both at national and international level.

Results from international multicenter studies on new drugs for osteoporosis including cathepsin K inhibitors and antisclerostin antibodies were promising.

At national level, 2013 was a bone year par-excellence. The updated Lebanese FRAX-Based Osteoporosis Guidelines were launched during 2013 and OSTEOS carried several scientific activities and expanded its outreach in various areas of Lebanon. Also, many events took place in Beirut during the fall and were very successful. These included the ISCD-IOF densitometry course for technicians and clinicians and the 5th annual meeting of our society, where distinguished local and international speakers updated us on topics related to women’s bone health across reproductive and menopausal life, as well as the relationship between non-communicable diseases and bone health.

Our hope is that 2014 be as successful as 2013 at bone health level, most importantly we hope that the New Year brings stability and peace to our beloved country.

Happy New Year

Asma Arabi, MD, MSc

Editor-in-Chief: Asma Arabi, M.D, MSc Guest Editors: Hala Ahmadieh, MD and Nancy Nakhoul, MD

President Faysal El-Kak, MD

Founding President Ghada El-Hajj Fuleihan, MD, MPH

Vice-President Georges Halaby, MD

Treasurer Jad Okais, MD

Executive Committee Rafic Baddoura, MD, MPH Ghada El-Hajj Fuleihan, MD, MPH Jad Okais, MD Muhieddine Seoud, MD

Non Voting Members Assaad Mohanna, MD Walid Saghir, MD Imad Uthman, MD

Newsletter of the Lebanese Society for Osteoporosis and Metabolic Bone Disorders

F a l l I s s u e , 2 0 1 3 # 6 . 3

OSTEOS NEWSLETTER

M i s s i o n o f O S T E O S

Executive Board

Layout & Design by Sarine El Daouk

Bisphosphonates (BPs) are known to reduce the risk of fracture with a long term beneficial effect. However BPs reduce bone remodeling and might “freeze” the skeleton leading to the accumulation of microcracks over time and fractures (also called stress fractures). 59 patients with atypical fractures were identified among 12,777 Swedish women aged 55 years or older who sustained a fracture of the femur in the year 2008. The age-adjusted relative risk of atypical fracture with any use of BPs was 47.3 and the difference in the risk of atypical fracture between users and nonusers of BPs was 5 cases (95% CI, 4 to 7) per 10,000 patient-years, corresponding to an average number needed to harm of 2000 per year of use. This risk was noted to be higher with a longer duration of use. After drug withdrawal, the risk decreased by 70% per year since the last use.

Schilcher Jörg, Michaëlsson Karl, Aspenberg Per, N Engl J Med 2011;364:1728-37.

O s t e o p o r o s i s t h e r a p i e s : B e n e f i t s v e r s u s H a r m s

Page 2 O S T E O S N E W S L E T T E R

Bisphosphonate Use and Atypical Fractures of the Femoral Shaft

Early diagnosis of Atypical Femoral Fracture Using DXA scans

The Task Force Report of the ASBMR 2010 listed five major criteria for the diagnosis of atypical femoral fractures (AFF). AFF often have a prodrome of pain and tenderness at the fracture hence the opportunity for early detection. In the current study McKenna et al studied if incomplete AFF may be detected using DXA scan by extending the length of the femur image. 257 patients over 50 years of age taking bisphosphonates (BPs) for more than 5 years who presented for routine DXA, had an extended hip scan performed bilaterally in order to view the extra length of the femoral shaft. 19 (7.4%) patients were referred for a plain X-ray of pelvis with imaging of lateral femur for suspected abnormalities in the lateral aspect of the femur (namely “flare” or “beaking”). X-ray showed evidence of AFF in 7 out of 19 cases (2.7%) and additional abnormality (osteochondroma, abnormal lucency, and cortical thickening) in 5 out of 19 cases (2%). On multivariable analysis, duration of BPs therapy was the only factor associated with AFF (OR=1.35, 95%CI=1.04-1.76).

McKenna et al, ASBMR 2014, Presentation Number: 1096.

Effect of Teriparatide on healing of incomplete Atypical Femur Fracture

Although incomplete non-displaced Atypical femoral fractures are diagnosed more frequently, their treatment remain unclear. In this study, 22 postmenopausal women (mean age 65.9 years) with incomplete AFF were treated with teriparatide for an average duration of 18.8 months (1-36). The average length of bisphosphonate use was 12.0 years (3.4-28). Of the 22 patients, 3 underwent prophylactic surgical repair. Follow-up imaging every 6 months with CT scans and plain radiographs were done for the remaining 19 cases. Of these 19 AFFs, 2 had healed, 5 were healing, 12 were stable, and none had worsened at last follow-up. However, 4 patients developed new lucency lines in the same femur as their original incomplete AFF despite teriparatide therapy, hence a positive impression on the possible role of teriparatide in the healing of non-displaced AFF.

Cheung et al ASBMR 2014 Presentation Number: 1080.

C a l c i u m s u p p l e m e n t a t i o n : B e n e f i t s v e r s u s H a r m s

Page 3 F a l l I s s u e , 2 0 1 3 # 6 . 3

Because of the conflicting results with regards to calcium supplements and calcium intake, patients and physicians feel confused with regards to this issue. A recent review published in the New England Journal of medicine summarized the current understanding of calcium intake as it relates to fracture risk and discussed concerns with regards to the safety of calcium supplements. Adequate calcium intake was found to be important for skeletal health at all ages. Consumption of calcium-rich foods and beverages is the preferred approach to get adequate calcium intake and there is insufficient evidence to recommend routine calcium supplementation in community-dwelling adults, but supplements should be considered when dietary intake is inadequate but supplementation above 2500 mg per day (2000 mg per day in persons >50 years of age) should be avoided. Calcium supplements usually have few side effects, although constipation and bloating are common and nephrolithiasis occurs infrequently. Recent studies have raised concern about an increased cardiovascular risk with the use of calcium supplements, but the findings are inconsistent and inconclusive and still debatable.

Bauer Douglas N Engl J Med 2013;369:1537-43.

Controlled trials suggest that calcium supplement use might increase cardiovascular events and mortality, use of dietary calcium intake, calcium supplements and mortality was assessed among men > 65 in this prospective MrOS. It was shown that calcium intake was not associated with total or cardiovascular mortality (p trend = 0.51 and 0.79, respectively). Calcium supplement use was also not associated with total mortality (RH =1.06, CI: 0.96, 1.18) or cardiovascular mortality (RH = 1.00, CI: 0.83, 1.20).

Douglas B. et al., ASBMR 2014, Presentation Number: 1001

Potential Benefits Versus Risks of Dietary Calcium and Supplemental Calcium Supplements

Dietary and Supplemental Calcium Intake and Mortality in men: MrOS Study

A collaborative pre-planned meta-analysis of randomised controlled trials published in the English language including women over 50 years of age who used calcium supplementation > 1 year with or without vitamin D and their effects on all-cause mortality and an adjudicated ischemic heart disease (IHD) hospitalizations or death that include angina, myocardial infarction and chronic ischemic heart disease found that data does not support the concept that calcium supplementation with or without vitamin D would increase the risk of ischemic heart disease or total mortality in elderly women. The trial level relative risk (RR) data for the 4,646 deaths in 59,844 participants yielded a RR of 0.96 (0.91-1.02), P = 0.1 with low heterogeneity (I² = 0%) for those randomized to supplements. The trial level RR for the 3,334 ischemic heart disease events in 46,843 participants was 1.02 (0.96-1.09), P = 0.5 (I² = 0%) while the trial level RR for the 1,097 myocardial infarction events in 49,048 participants was 1.09 (0.89-1.33), P = 0.21 with low heterogeneity (I² = 28%).

Lewis J. et al, ASBMR 2014, Presentation Number: 1002

The Cardiovascular Safety of Calcium Supplementation With or Without Vitamin D: A Meta-analysis from Randomised

Controlled Trials

Page 4 O S T E O S N E W S L E T T E R

The main complication of vitamin D toxicity is hypercalcemia. The aim of this large population based study was to identify the incidence of hypervitaminosis D that may complicate vitamin D supplementation and its association with hypercalcemia. 20,308 total 25-hydroxyvitamin D *25OHD+ levels were identified from the Rochester epide-miology project databases from 2002-2011, hypercalcemia defined as serum calci-um>10.1mg/dl or ionized calcium >5.3 mg/dl was considered associated with hyper-vitaminosis D if measured within 3 months of 25(OH)D measurement.

Of the total number of measurements, 1885 (9.3%) had 25 OHD level >50 ng/ml, 133 (0.7%) had 25OHD level ≥80ng/ml and 44 unique persons (0.2%) had their levels ≥100 ng/ml. The incidence of hypervitaminosis D increased from 10 per 100,000 in

2002 to 260 per 100, 000 in 2011 mainly in patient aged ≥ 65years and in females. 960 serum calcium were measured within 3 months of 25OHD level, 19% had hypercalcemia. 25OHD values were not significantly related to serum calcium values (p=0.7) or the risk of hypercalcemia.

Dudenkov D et al, ASBMR 2014, Presentation Number 1098

Incidence of Vitamin D Toxicity: A Population-Based Study

The association between low vitamin D and cardiovascular disease has been widely studied, but the data remain inconclusive and all studies were based on a single vit D measurement.

In this prospective population-based German cohort study, the association of 25(OH)D with fatal and nonfatal CVD in the same study population was assessed using repeated 25(OH)D measurements and competing risks analysis in 9949 men and women, aged 50 to 74 years. Data were collected at baseline and at follow-up including survival status, were collected after 2, 5, and 8 years. 25(OH) D was measured in blood samples collected at baseline and the 5-year follow-up visit. Main Outcomes included CVD, coronary heart disease (CHD), and stroke, in total and differentiated into fatal and nonfatal events.

Overall, 854 study participants had a nonfatal and 176 a fatal CVD event during 8 years of follow-up. Comparing subjects with 25(OH) D levels below 30 nmol/L and above 50 nmol/L resulted in a hazard ratio of 1.27 (95% CI 1.05-1.54) for total CVD and 1.62 (95% CI 1.07-2.48) for fatal CVD in a model adjusted for important potential confounders. No significant association for nonfatal CVD was observed. In dose-response analysis, an increased cardiovascular risk at 25(OH)D levels below 75 nmol/L was observed. Results for CHD and stroke were comparable to the results obtained for the composite outcome CVD and supported the evidence that low 25(OH)D levels are associated with moderately increased risk of CVD.

Perna L et al, J Clin Endocrinol Metab,2013; 98:4908-15

V i t a m i n D : B e n e f i t s v e r s u s H a r m s

Serum 25-hydroxyvitamin D and incidence of fatal and nonfatal cardiovascular events

Long-term vitamin K inadequacy has been indicated as an independent but

modifiable risk factor for the development of age-related diseases, including

osteoporosis, since vitamin K is important for the posttranslational car-

boxylation of glutamateintoγ-carboxyglutamate (Gla) residues in so called Gla

-proteins. It was earlier shown that 3-year high-dose vitamin K1

(phylloquinone) and K2 (short-chain menaquinone-4) supplementation

improved bone health after menopause. Because of the longer half-life and

greater potency of the long-chain MK-7, this study extended these

investigations by measuring the effect of low-dose vitamin K2 MK-7

supplementation on bone health. MK-7 intake(180 μg/day) given to healthy

postmenopausal women (n=244) for 3 years significantly improved vitamin K status and decreased the age-related decline in

BMC and BMD at the spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7.

Moreover it was shown that MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the

mid-site of the vertebrae.

Knapen M. & Drummen N. Smit E. &Vermeer C, Theuwissen E. Osteoporos Int,2013; 24:2499–250.

Page 5 F a l l I s s u e , 2 0 1 3 # 6 . 3

In a post-hoc analysis of 2 open label studies comparing denosumab 60mg

subcutaneously every 6 months with bisphosphonates (BP) 150mg monthly

(Ibandronate or residronate) in post menopausal women ≥55 years suboptimally

treated with bisphosphonates, with mean age of 67 (SD 7.4) years over a period of

12 months, and in the subset on high fracture risk subjects defined as having ≥1 risk

criteria (advanced age, low BMD, prior osteoporotic fracture, high baseline sCTX-1),

Denosumab significantly increased BMD at 12 months compared to BP (Ibadronate

and Residronate) at the total hip (2.2% vs 0.8%), femoral neck (1.8% vs 0.3%) and

lumbar spine (3.8% vs 1.4%) (p <0.0001 for all). Adverse events were similar between

groups.

John H et al, ASBMR 2014, Presentation Number: 1018.

U p d a t e s i n O s t e o p o r o s i s m a n a g e m e n t

Denosumab versus bisphosphonates after oral Bisphosphonate

Menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women.

It is already known that there is an increased risk of osteoporosis and fractures in patients with several gastrointestinal diseases, including ulcerative colitis, Crohn’s disease and celiac disease; therefore this study was done to investigate whether this association exists in patients with irritable bowel syndrome (IBS) using the 2008 US Nationwide Emergency Department Sample database.

It was found that the risk of osteoporosis in patients with IBS was significantly increased compared with controls (OR 4.2, 95% CI 4.2–24.3). Moreover, significantly higher risk of osteoporotic fractures were found in IBS patients (OR 2.3, 95% CI 2.2–22.4). Comparison with other gastrointestinal disorders indicated that IBS was associated with a higher risk of osteoporosis and osteoporotic fractures than Crohn’s disease and ulcerative colitis, but a lower risk than that associated with coeliac disease.

On the basis of these findings, the authors suggest that screening measures should be put in place for patients with IBS to identify those with osteoporosis and prevent fractures. The cause is poorly understood but psychosocial factors, abnormal gut motility and changes in the gut bacterial flora have been implicated in the pathogenesis of IBS. Potential mechanisms that could

contribute to loss of BMD in patients with IBS include increased circulating levels of cytokines such as IL-1β, tumor necrosis factor, IL-6 and IL-8, and an increase in the mast cell population of the small and large bowel mucosa, which results in an increased production of serotonin and histamine. In addition, many patients with IBS have to avoid dairy products because of lactose intolerance, and as a result have a reduced intake of calcium. Finally, the use of selective serotonin reuptake inhibitors to treat IBS might increase the risk of osteoporosis and osteoporotic fractures.

Compston J.E. Nat. Rev. Endocrinol, 2013;9: 8–9.

O t h e r d i s e a s e s w i t h h i g h o s t e o p o r o s i s r i s k

Page 6 O S T E O S N E W S L E T T E R

Rheumatoid arthritis (RA) is a systemic auto-immune inflammatory

disease characterized by arthritis involving the small joints of the

hands and feet. Extra-articular signs and symptoms can occur

including nodules, vasculitis, pulmonary, and ocular manifestations.

Generalized bone loss, which may lead to an elevated fracture risk

due to its active inflammation and the wide spectrum of cytokines

leading to bone and cartilage destruction and the reduced quality of

life. High disease activity and inflammation, immobility, and

glucocorticoid use substantially increase fracture risk. There have

been new insights on the links between the immune system and the

bone system, the field of osteoimmunology. The receptor activator

of nuclear factor κB ligand/osteoprotegerin pathway (RANKl/OPG) is

one of the most important pathways which is upregulated by

inflammation. Modern treatment of RA with biologics, for example, TNFα-blocking agents and combination therapy of

conventional disease-modifying antirheumatic drugs have led to clinical remission and it was found that both local and

generalized bone loss were absent or minimal in those patients who achieved clinical remission. It would be attractive to

further investigate the effectiveness of potent antiresorptives, such as zoledronic acid or denosumab in those patients with RA

whose disease activity is not adequately controlled.

Güler-Yüksel M.V., Lems W.F. Osteoporos Int, 2013; 24:2541–2553.

Can bone loss in rheumatoid arthritis be prevented?

Risk of osteoporotic fractures in irritable bowel syndrome.

Page 7 F a l l I s s u e , 2 0 1 3 # 6 . 3

D e n s i t o m e t r y c o r n e r

The diagnosis and management of osteoporosis have been improved by the development of newquantitative

methods of skeletal assessment, tools that were used for assessing and analysing images and accordingly

guidelines and standards have been published to help clinicians in knowing how to use these techniques

effectively.

DualenergyX‑ray absorptiometry (DXA) is currently the most widely utilized method for clinical diagnosis of

osteoporosis and will remain so for the foreseeable future. The WHO 10-year fracture risk assessment tool

(FRAX®) will improve clinical use of DXA and aid in deciding on the need for therapeutic intervention.

Improved reportingof radiographic features that suggest osteoporosis and the presence of vertebral

fracture, which are powerful predictors of future fractures, could increase the frequency of appropriate

DXA referrals. Quantitative CT remains is currently predominantly a research tool, but has advantages over

DXA because it allows the measurement of volumetric density and is capable of separating measures of

cortical and trabecular bone density, and evaluation of bone shape and size. High resolution imaging, using

both CT and MRI, has been introduced to measure trabecular and cortical bone microstructure. Although

these methods provide detailed insights into the effects of disease and therapies on bone, they are

technically challenging and not widely available, so they are unlikely to be used in clinical practice.

Adams, J. E et al, Nat. Rev. Endocrinol, 2013; 9: 28–42.

Page 8 O S T E O S N E W S L E T T E R

Upcoming Meetings and Events

Date Event Venue/link

International events

Jan 17, 2014 XXVIIème Journée Scientifique du Goupe de Re-

cherche et d’Information sur l’Osteoporose GRIO

Les Salons de l'Aveyron PARIS

http://www.grio.org

Feb 20-22, 2014 IOF-ISCD Skeletal Health Orlando, Florida USA

www.iof-iscd-meeting.org

Apr 2-5, 2014 World Congress on Osteoporosis, Osteoartthritis &

Musculoskeletal Diseases

Seville-Spain

http://www.wco-iof-esceo.org

May 17-20, 2014 41st European Calcified Tissue Society Congress Prague, Czech Republic

http://www.ectscongress.org

Jun 21-24, 2014 ICE/ENDO joint meeting Chicago, Illinois, USA

https://www.endocrine.org/meetings

Sep 14-17, 2014 ASBMR annual meeting Houston, Texas, USA

http://www.asbmr.org/Meetings

Local events

Jan 24-25, 2014 ISCD Osteoporosis Academy Gefinor Rotana, Beirut Lebanon

The Lebanese Society for Osteoporosis and Metabolic Bone Disorders

OSTEOS held its 5th annual meting in Beirut in December 6-7, 2013. During

this very rich two day meeting, distinguished local and international

speakers shared with us the most recent updates in hot topics in

osteoporosis and metabolic bone disorders.

During the first day of the meeting, the speakers took us in a scientific journey on women’s bone health across reproductive

years from the effect of contraceptive agents on bone health, to the bone mineral density change in PCOS, not to forget

bone health during pregnancy. Women’s health during postmenopausal year including the WHI and its implications on the

future of HRT in our part of the world, as well as new indications of SERMs therapy were discussed in the afternoon. In his

key note lecture, Professor Ian Reid, from the University of Auckland reviewed and discussed controversies concerning

efficacy and safety of old and new therapies. Then, Professor Rene Rizzoli from the University of Geneva provided us with

evidence-based care pathways to prevent skeletal related events and bone loss in cancer patients. The first day was closed

by the lecture of Professor Angela Cheung from the University of Toronto and Dr Leon J Schurgers from Maastricht

University who updated us on the very important role of vitamin K2 in maintaining bone health.

The second day of the meeting was the oyster that contained the finest pearls on bone health in non communicable

diseases such as epilepsy, diabetes, chronic kidney diseases, obesity and thyroid disorders, thus providing colleagues in all

specialties with evidence-based information that help them deliver the best of care to their patients.

We would like to thank all our colleagues who attended the meeting, hope they enjoyed it and promise them to keep same

standards at our future meetings.

A w o r d a b o u t O S T E O S 5t h

a n n u a l m e e t i n g