Download Vertebral fractures - Osteoporosis Canada

Osteoporosis Canada
Winter 2008 • vol. 12 no. 1
Ostéoporose Canada
osteoporosis
update
a practical guide
for Canadian physicians
Vertebral fractures
Guidelines promote improved
diagnosis and reporting
Renal safety of bisphosphonates
Teriparatide (PTH) for
severe osteoporosis
Drug coverage in your province
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NEW!
IN POSTMENOPAUSAL OSTEOPOROSIS
ACTONEL 75 mg
To help fit her lifestyle,
ACTONEL 75 mg provides a new
dosing option: two consecutive
days per month.2
ACTONEL
helps you
watch her back
1,2
And her hip/pelvis,
clavicle, humerus,
leg and wrist *
1,2 †
* Composite score for nonvertebral fractures.
† Vertebral fractures: ACTONEL 5 mg
2.4% vs. placebo 6.4%; p<0.001, 0-1 year.
Nonvertebral fractures: ACTONEL 5 mg
5.2% vs. placebo 8.4%; p=0.02, 0-3 years.
ACTONEL is indicated for the treatment and prevention of osteoporosis
in postmenopausal women. ACTONEL 75 mg two consecutive
days per month is indicated for the treatment of osteoporosis in
postmenopausal women.
ACTONEL is contraindicated in patients with known hypersensitivity to
any component of the prescribed product. ACTONEL is contraindicated
in patients with hypocalcemia. These and other disturbances of
bone and mineral metabolism should be effectively treated before
starting ACTONEL. Adequate intake of calcium and vitamin D is
important. ACTONEL is not recommended for use in patients with
severe renal impairment (creatinine clearance <30 mL/min).
Since some bisphosphonates have been associated with upper
gastrointestinal disorders, careful attention should be paid to the
ACTONEL dosage and administration instructions especially in patients
with a history of esophageal disorders. ACTONEL should be taken
on an empty stomach at least 30 minutes before the first food, drink
(other than plain water) and/or medication of the day, while in an
upright position with sufficient plain water (≥120 mL). Patients should
also not lie down for at least 30 minutes after taking ACTONEL.
In postmarketing reporting, osteonecrosis of the jaw has been
reported in patients treated with bisphosphonates. Clinical judgement,
based on individual risk assessment, should guide the management
of patients undergoing dental procedures.
Musculoskeletal pain, rarely severe, has been reported as a common
adverse event in patients who received ACTONEL for all indications.
In clinical trials, the overall incidence of adverse events with ACTONEL
5 mg daily was comparable to placebo. The most commonly reported
adverse events were (placebo vs. ACTONEL 5 mg) abdominal pain
(3.3% vs. 4.1%), dyspepsia (4.8% vs. 5.2%) and nausea (5.0% vs.
4.8%). The overall safety and tolerability profile of ACTONEL 35 mg
Once-a-Week is similar to that of ACTONEL 5 mg daily.
The overall safety profile, including the incidence and pattern of upper
gastrointestinal events of ACTONEL 75 mg on two consecutive days
per month, is similar to that of ACTONEL 5 mg daily. Vomiting was
reported in more ACTONEL 75 mg-treated patients than 5 mg daily
(1.1% vs. 1.0%, respectively).2
Please refer to accompanying Prescribing Information for full dosing
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editorial
osteoporosis
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update
Improved patient care:
the common goal
Osteoporosis Update is published by
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Julie M. Foley, President & CEO
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Mairi MacKinnon, Managing Editor
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Louis-Georges Ste-Marie,
MD, CPSQ is an endocrinologist and Director of
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Diseases Laboratory at
the Centre de recherche
du Centre hospitalier de
l’Université de Montréal,
Hôpital Saint-Luc. He is
Associate Professor of
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editorial board
Angela M. Cheung, MD, PhD, FRCPC
University of Toronto
Sidney Feldman, MD, FCFP
University of Toronto
David A. Hanley, MD, FRCPC
University of Calgary
Anthony B. Hodsman, MB, BS, FRCPC
University of Western Ontario
Stephanie Kaiser, MD, FRCPC
Dalhousie University
Gregory Kline, MD, FRCPC
University of Calgary
Heather McDonald-Blumer, MD, FRCPC
University of Toronto
Suzanne Morin, MD, FRCPC
McGill University
Robert Sabbah, MD, FRCSC
Université de Montréal
Kerry Siminoski, MD, FRCPC
University of Alberta
Louis-Georges Ste-Marie, MD, CPSQ
Université de Montréal
© 2008 Osteoporosis Canada
No articles may be reprinted without permission.
Views expressed by the authors are not
necessarily endorsed by Osteoporosis Canada.
Osteoporosis Update is made possible with the
assistance of unrestricted educational grants
from the following sponsors:
ore than 65% of vertebral fractures go undetected. Physician
awareness of the importance of these fractures, which are
associated with a major risk for future fractures and a significant predictor of morbidity and mortality, is crucial. Given the
increasing evidence of this care gap, Osteoporosis Canada and the
Canadian Association of Radiologists published a set of recommendations to promote and facilitate the diagnosis and reporting of vertebral
fractures. In the feature article on page 4 of this issue, we present a
summary of the document’s key points to guide clinicians and healthcare providers involved in the care of individuals with osteoporosis.
On page 6, experts from the Scientific Advisory Council (SAC)
Drs. Anthony Hodsman and Sophie Jamal answer timely questions
on the effect of long-term bisphosphonate therapy on the kidneys
and the use of the bone-building agent teriparatide (PTH [Forteo®])
for severe osteoporosis. Next, a special section on provincial formularies (page 7) provides physicians across the country useful
information on which osteoporosis drugs are available through
benefit programs in their region.
Finally, on page 9, we wish to congratulate the 2007 winner of the
Lindy Fraser Memorial Award, Dr. Anthony Hodsman, for his outstanding contribution to osteoporosis research and education over the
years. Dr. Hodsman had a leadership role as Chair of the SAC from
2003 to June 2006, and has published extensively in the basic science
and clinical fields, as well as on the application of clinical practice
guidelines in osteoporosis. We also take the opportunity to highlight
some of the important Canadian studies presented in September 2007
at the American Society for Bone and Mineral Research (ASBMR)
Annual Meeting. The contribution of Canada’s researchers at this
meeting was substantial. While we are unable to mention all of them
here, we laud all their efforts, which are so vital to the goal of improving
treatment and care for the 1.4 million Canadians with osteoporosis.
We hope you will find this issue informative and useful in your
daily practice. The SAC welcomes your feedback — please send any
questions or comments to [email protected].
Eli Lilly Canada Inc.
P&G Pharmaceuticals and sanofi aventis
The financial support received from sponsors
does not constitute an endorsement by
OsteopoRosis Canada of any of the
sponsors’ products or services.
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Bisphosphonate and calcium concerns
In our next issue, the SAC will address recent reports on the use of oral
bisphosphonates and risk of aseptic osteonecrosis, as well as a possible risk of
cardiovascular events in older women who take calcium. Meanwhile, physicians
are advised to consult www.osteoporosis.ca for updated information.
osteoporosis update
Winter 2008
3
f eatu re
Vertebral fracture
diagnosis
Recommendations to help reduce future risk
VI
ertebral fractures, the most common type of osteoporotic fractures, are a major risk factor for future
fractures and a significant predictor of morbidity
and mortality. While early detection can lead to further
investigation and appropriate therapy that helps cut the
risk of future fractures, increasing evidence shows that
these important clinical markers of osteoporosis are both
underdiagnosed and inadequately followed up.
The Scientific Advisory Council of Osteoporosis Canada,
together with the Canadian Association of Radiologists,
created a multidisciplinary working group to address
this care gap. Their recently published rec­ommendations
(Lentle BC, Brown JP, Khan A et al. Recognizing and
reporting vertebral fractures: reducing the risk of future
osteoporotic fractures. CARJ 2007;58:27-36) stress the
need for physician awareness of the importance of vertebral fracture diagnosis in assessing future osteoporotic
fracture risk. While not advocating widespread radio-
Key messages
• Radiologists should identify and report vertebral fractures incidental to
radiologic exams done for other reasons.
• The Genant semiquantitative method (measuring loss of vertebral endplate parallelism, cortical interruptions, and changes in the anterior, midbody and posterior heights of vertebral bodies) is most effective for
assessing vertebral fracture from lateral spine or chest radiographs; Grade
II and III fractures should receive the most emphasis.
• When spine radiographs are performed, anteroposterior exams may assist
in the initial evaluation.
• Follow-up may only require single lateral views of the thoracic and lumbar
spine, including T4 to L4 vertebrae.
• Dual-energy x-ray absorptiometry (DXA) exams that include lateral spinal
morphological assessments (VFA) may contribute to fracture recognition.
• All physicians should be educated on the clinical significance of vertebral
fracture recognition as a potential indicator of future risk of osteoporotic
fracture, with its associated morbidity and mortality.
4
osteoporosis update
Winter 2008
graphic screening (due to reasons of cost and radiation
exposure), the document concludes that it is to patients’
benefit that radiologists report all vertebral fractures seen
on chest or other radiographs, regardless of the initial purpose of the examination, and, where appropriate, make
recommendations for further evaluation.
The recommendations, reached by consensus, were
reviewed and endorsed by the following organizations:
• Canadian Association of Nuclear Medicine
• Canadian Association of Radiologists
• Canadian Orthopaedic Association
• Canadian Panel of the International Society for
Clinical Densitometry
• Osteoporosis Canada
• Society of Obstetricians and Gynaecologists of
Canada
The full text, as well as a Powerpoint slide presentation,
are available at www.osteoporosis.ca, in the Health Professionals section. This article presents a brief summary.
Impact of vertebral fractures
Both clinical and occult vertebral fractures are associated
with significant health consequences. Clinical fractures,
detected when patients present with back pain, account
for approximately one-third of osteoporotic vertebral
fractures. The rest are occult fractures; they do not cause
severe pain and consequently go undiagnosed in routine
medical evaluations that do not include x-rays.
Vertebral fractures can lead to deterioration of physical function and decreased ability to perform activities of
daily living. Effects include:
• chronic back pain
• reduced range of motion
• slower gait
• impaired pulmonary function
• higher likelihood of disability
• loss of independence
• social isolation
• lower quality of life
Vertebral deformities are associated with a marked
increase in the risk of additional fractures, including hip
fractures, and also with higher short- and mid-term
mortality rates. Five-year mortality rates following ver­
tebral fractures are comparable to those following hip
fracture. Since physicians and healthcare providers
involved in the care of these patients may not always
appreciate the future implications of vertebral fractures,
increased awareness is crucial.
Underreporting of vertebral fractures:
clinical implications
More than 65% of spinal fractures go undetected. To
compound this problem, studies reveal that radiology
reports often neglect to mention fractures evident on
chest or other radiographs done for other reasons. In
one study of 934 women aged 60 years or over who
had chest x-rays, 132 of the women were diagnosed
with one or more spinal fractures using Genant’s semiquantitative criteria (the most widely used criteria for
defining vertebral fracture), but only 65 cases (49%)
were reported. Further, the diagnosis was entered in
the medical record of only 23 (17%) of the patients,
and only 25 of these women with fractures (19%)
received osteoporosis treatment.
A similar Canadian study of emergency department
radiographs looked at a population comprised of 47%
women, mean age 75 years, 46% of whom were admitted to hospital. According to the reviewing radiologist,
the prevalence of moderate to severe vertebral fractures
(Genant Grades II and III) was 22%; only 55% of these
were mentioned in the official radiology reports.
In an analysis of data from the IMPACT (Improving
the Measurements of Persistence on Actonel Treatment)
trial, Delmas et al identified underdiagnosis of vertebral
fractures as a worldwide problem. False-negative rates of
fracture reporting in women aged 65–80 years ranged
from 29.5% to 46.2% in various countries, while the
false-positive rate, at 5%, was not a significant issue.
For clinicians, including radiologists, these data
present a considerable opportunity for better patient
management through prevention of the disease and
disability associated with fractures. It is clearly to
patients’ benefit that radiologists report vertebral fractures detected on chest or other radiographs, no matter
how incidental to the primary reason for the examination. Bone mineral density (BMD) testing should be
considered if a fracture is found. Precise indication by
the radiologist of the grade of fracture and vertebrae
involved will be useful to the clinician.
Radiographic techniques
To date, vertebral radiographs provide the best simple
method for assessing the presence of vertebral fractures.
In the absence of localized pain, no adequate alternative
exists to indicate the need for more sophisticated examinations such as computed tomography (CT) or magnetic
resonance imaging (MRI) of the spine.
It is to patients’ benefit that radiologists report
all vertebral fractures seen on chest or other
radiographs, regardless of the initial purpose of
the examination, and, where appropriate, make
recommendations for further evaluation
For the initial assessment of spinal osteoporotic fractures, both the anteroposterior and lateral projections of
the thoracic and lumbar spines are advised. For follow-up,
only lateral radiographs are required as these are the
most effective in detecting osteoporotic fractures.
Tools to measure bone quality could improve fracture
risk assessment and follow-up. At present, osteoporosis
is diagnosed based on BMD measurements or the
existence of a low-trauma fracture, the history of
which provides the simplest measure of bone quality.
As appreciation of the importance of diagnosing
as­­ymptomatic fractures grows, makers of some central
x-ray-based densitometers are adding software to image
relevant spinal segments (lateral imaging, T4 to L4).
Vertebral fracture assessment (VFA, also described by
various manufacturers as instant vertebral assessment,
lateral vertebral assessment and dual-energy vertebral
assessment) provides lower-resolution images that
are not subject to projection distortion. While this
technology is promising, further research is needed
before VFA is adopted for widespread clinical use.
(For more information on radiographic techniques,
see the full CARJ document.)
Tools to bridge the care gap
A care gap exists in the identification, reporting and
follow-up of vertebral fractures. Physician awareness of
the importance of vertebral fracture diagnosis in assessing
future risk is key. Chest radiographs are a valuable casefinding tool for assessing vertebral fractures. Radiologists
should recognize the need for reporting fractures seen
on these or other radiographs. Where appropriate, the
report should include recommendations for further evaluation (e.g. thoracic and lumbar spine radiographs and
DXA testing) to promote further action on the part of
the clinician. ●
Possible wording for reporting
vertebral fractures
Incidental note is made of fractures in the thoracic spine involving Tx, Tx’ and
Tx”. If these are low-trauma fractures, this finding strongly suggests that the
patient has osteoporosis and is very likely to sustain further fractures in the
next year. Further investigation and follow-up is strongly recommended.
osteoporosis update
Winter 2008
5
qu estions
&
answers
q.
Can long-term bisphosphonate treatment for osteoporosis be harmful to the kidneys? Which patients are at
risk, and what can be done to minimize the risk?
Dr. Anthony Hodsman responds: Nephrotoxicity
following intravenous (IV) bisphosphonates has been
reported with both pamidronate and zoledronic acid in
cancer patients, mostly in cases of multiple myeloma.
The complication is uncommon, but appears to be
related to high doses infused over relatively short time
periods (< 2 hours for pamidronate and < 15 minutes
for zoledronic acid).
To my knowledge, direct nephrotoxicity has not been
reported following the use of oral or IV bisphosphonates
in doses recommended or approved for osteoporosis.
While a 25% dose reduction for zoledronic acid as used
in cancer patients is advised (from 4 mg to 3 mg for
glomerular filtration rates [eGFR] < 40 ml/min), no
such reduction has been recommended for the unit dose
(5 mg) of once-yearly zoledronic acid for treating osteoporosis. Protocol amendments were introduced during
the Phase III Oncology trials of IV zoledronic acid based
on impaired renal function, but none were in place during the pivotal Phase III HORIZON trial in osteoporosis
patients. Renal function was carefully monitored in subgroups, and no differences in either efficacy outcome or
renal function were found between the treated and placebo groups. However, the Phase III clinical trials for all
bisphosphonates used as osteoporosis therapy excluded
patients with chronic kidney disease (creatinine clearance rate [eGFR] < 35 ml/min). There is therefore little
data about fracture prevention efficacy and long-term
adverse effects in these individuals. Bisphosphonate
labelling warns against using these drugs when the eGFR
is < 35 ml/min. Retrospective analysis of the Fracture
Intervention Trials (FIT) and pooled data from 9 risedronate studies revealed that approximately 10% of subjects
had severe renal impairment (eGFR < 30–45 ml/min),
and up to 45% had moderate renal impairment (eGFR
30–60 ml/min). In the post-hoc analyses, both alendronate and risedronate increased bone mineral density
(BMD) and prevented vertebral fractures regardless of
the degree of renal impairment, compared with placebo.
There were no apparent differences in adverse event rates
between subjects with normal or reduced renal function
with either oral bisphosphonate. While small increments
Dr. Anthony Hodsman founded the London Regional Osteoporosis Program,
and is currently Professor in the Department of Medicine at the University
of Western Ontario, in London.
Dr. Sophie Jamal is Medical Director and Director of Research of the Osteoporosis
Program at Women’s College Hospital, and Assistant Professor in the Division of
Endocrinology and Metabolism at the University of Toronto.
6
osteoporosis update
Winter 2008
in serum creatinine were observed during the 3-year FIT
study, these were similar both in individuals with and
without reduced renal function at the outset, as well as
in groups taking placebo and active drug.
It is important to remember that the clinical syndrome
of renal osteodystrophy (uremic bone disease associated
with progressive 2° hyperparathyroidism and phosphorus
retention) becomes manifest at eGFR < 30 ml/min.
Vitamin D deficiency becomes more frequent as general
health and nutrition deteriorate with advancing kidney
failure. Moreover, the diagnostic value of bone densitometry is invalid in such patients, since bone mineralization
is impaired by both the presence of hyperparathyroid
bone disease and osteomalacia, thus apparently lowering
the reported T-score. The management of patients with
apparent osteoporotic fractures — with advanced chronic
renal failure and/or on renal replacement therapy — is
a grey zone. While bisphosphonate therapy is tempting,
in the absence of any alternative treatment, physicians
should use these drugs in the knowledge that there is no
proof of efficacy in this patient group, either in improving BMD or preventing fractures.
To my knowledge, direct nephrotoxicity
has not been reported following the use
of oral or IV bisphosphonates in doses
recommended or approved for osteoporosis
The kidneys excrete approximately 50% of an administered bisphosphonate dose. The remainder is bound to
bone, where it exerts its selective action on osteoclasts.
While it would be reasonable to assume that a 50% dose
reduction should be employed when treating patients
with advanced renal failure, the available oral bisphosphonates in Canada have been used at higher than the
approved dose (for extended periods), without apparent
adverse effects. Unfortunately, there is no information
about the safety of conventional doses in advanced
renal failure, or comparative efficacy when using a
50% dose reduction (either reducing the unit dose or
extending the dosing interval).
The best advice I can give in this circumstance is to
refer the patient to a physician with experience in using
bisphosphonates in the setting of advanced renal failure.
Unfortunately, such specialists are few and far between.
References
Miller PD, Roux C, Boonen C et al. Safety and efficacy of risedronate
in patients with age-related reduced renal function as estimated by the
Cockroft-Gault method: a pooled analysis of nine clinical trials. J Bone
Mineral Res 2005;20:2105-15.
Jamal S, Bauer DC, Ensrud KE et al. Alendronate treatment in women
with normal to severely impaired renal function: an analysis of the fracture intervention trial. J Bone Mineral Res 2007;22:503-8.
q.
When should I consider teriparatide (Forteo®) as
first-line therapy for my postmenopausal patient with
very low BMD? Is it better to try other osteoporosis
therapies first? What should I advise patients taking
Forteo about calcium and vitamin D?
Dr. Sophie Jamal explains: Teriparatide is the only
anabolic agent available for treating osteoporosis. Ana­
bolics increase bone formation, activation frequency and
bone turnover, and induce microarchitectural changes to
create a new bone structure. The Canadian product
monograph for teriparatide suggests that is appropriate
for postmenopausal women with severe osteoporosis
who are at high risk of fracture or who have failed, or are
intolerant to, other therapies. These broad recommendations are sometimes curbed by cost concerns. For
example, the drug is not covered by Ontario Drug
Benefits and costs about $15,000 for the 18-month
treatment course. Practically speaking, teriparatide is
usually prescribed for patients who have had a low-trauma
fracture while adherent with a second-generation bisphosphonate, with no clinical or laboratory evidence
of secondary osteoporosis.
To date, there are no compelling data to suggest that
prior use of osteoporosis therapies influences the efficacy
p rovincial
of teriparatide on fracture reduction. Regardless of
whether teriparatide is prescribed following, or as a firstline agent prior to additional antiresorptive therapy,
once the course is completed patients should receive
maintenance antiresorptive treatment (Black DM et al.
NEJM 2005;353:555-65).
Administration of teriparatide is associated with transient increases in serum calcium about 4 to 6 hours after
dosing, but sustained hypercalcemia is unusual. A large
randomized trial of teriparatide for postmenopausal
women with osteoporosis in which all patients received
calcium (1000 mg) and vitamin D (400–1200 IU) reported
that mild hypercalcemia (serum calcium > 2.6 mmol/L)
based on samples obtained approximately a month after
treatment was observed in 2% of women on placebo
and 11% of women receiving 20 mcg of teriparatide
(Neer RM et al. NEJM 2001;344:1434-41). In the majority
of cases, reducing calcium intake corrected the hypercalcemia. It is also important to note that women who
did not have hypercalcemia in the first 6 months of
treatment seldom had it later. Based on this data, it
seems rea­sonable to advise patients to continue taking
the rec­ommended amounts of calcium and vitamin D.
Fasting serum calcium, measured 24 hours after the last
teriparatide dose, should be monitored periodically at least
for the first 6 months of therapy and if elevated, patients
should stop or reduce their calcium supplements. ●
f ormularies
Osteoporosis drug coverage in Canada
P
I
rovinces are responsible for deciding which medications
(ap­­proved by Health Canada) to include in their drug benefit
plans. Provinces provide selective drug coverage for eligible
groups, including individuals over 65 years of age and those on social
assistance and disability. Provincial formularies list which drugs are
available, either as general or restricted benefits:
• General benefits (open listing) require no special criteria or
paperwork.
• Restricted benefits require that individuals meet certain clinical
criteria. In general, the physician must submit a special form
along with the patient’s prescription.
Certain osteoporosis medications (e.g. etidronate [Didrocal®] and
hormone [estrogen] replacement therapy) are listed as general benefits
in most provincial formularies. The table on page 8 outlines the status
of the newer therapies on provincial formularies across the country. In
general, where generic versions of a drug are available, these will be
substituted and the lesser cost reimbursed. Patients who choose to stay
on the brand version instead of accepting the generic must pay the
difference. The whole cost may be covered if the physician specifies
the brand version only, but in this case the prescription must be
accompanied by a completed special authorization request form. ●
Continued on page 8
osteoporosis update
Winter 2008
7
Formulary listings for osteoporosis drugs
This chart reflects listings for use in osteoporosis patients. Listings of these drugs may differ for other conditions.
Coverage is under constant review and is subject to change.
Selective estrogen
receptor modulators (SERMs)
Calcitonin
Bisphosphonates*
Risedronate
Raloxifene (Evista®): Miacalin®: nasal
oral 60 mg/d
spray 200 IU/d
(Actonel®): oral 5
mg/d; 35 mg once a
(generics available)
week; 75 mg/mo on
2 consecutive days;
Actonel + calcium
Teriparatide (PTH)
Forteo®: subcu­
taneous injection
20 mcg/d, 18
months maximum
Alendronate
(Fosamax®): oral
10 mg/d; 70 mg
once a week
(generics available)
Alendronate 70 mg
plus vitamin D3
2800 IU weekly
(Fosavance®)
BC
SA
NL
SA (75 mg NL;
Actonel + calcium
under review)
SA
NL
NL
AB
SA
NL
SA (75 mg, Actonel
+ calcium NL)
SA
SA (calcitonin solution regular benefit)
NL
SK
EDS
NL
EDS (75 mg, Actonel
+ calcium NL)
EDS
EDS
NL
MB
EDS (Part 3)
NL
EDS (Part 3)
(75 mg, Actonel +
calcium NL)
EDS (Part 3)
EDS (Part 3)
NL
ON
General benefit
General benefit
General benefit
(75 mg, Actonel +
calcium NL)
LU
Miacalcin NL;
(calcitonin solution
general benefit)
NL
QC
Open
NL
Open (75 mg NL)
Open
Open
PE
NB
SA
NL
SA (75 mg under
review; Actonel +
calcium NL)
SA
SA (calcitonin
solution general
benefit)
NL
NS
EDS
NL
EDS (75 mg, Actonel
+ calcium NL)
EDS
EDS (calcitonin solution general benefit)
NL
PEI
NL
NL
NL
NL
NL
NL
NL
SA
NL
SA (75 mg, Actonel
+ calcium NL)
SA
SA
NL
YT
EDS
NL
EDS (75 mg, Actonel
+ calcium NL)
EDS
NIHB
LU
NL
LU (75 mg, Actonel
+ calcium NL)
LU
Province
*Note: Zoledronic acid (Aclasta®) 5 mg, a once-yearly bisphosphonate given
by 15-minute infusion by a certified medical professional, was approved on
October 30, 2007 for the treatment of postmenopausal osteoporosis. While it
is currently covered by the majority of provincial drug benefit plans (except
BC and NL) for the treatment of Paget’s disease, it is not covered for the
treatment of osteoporosis.
EDS (calcitonin
solution listed)
LU
NL
NL
SA: Special authorization
NL: Not listed in the formulary (i.e. not a benefit)
EDS: Exception drug status
PE: Patient of exception, under RAMQ but not Québec Basic Prescription Drug Insurance Plan
NIHB: Non-Insured Health Benefits, a federal health benefit plan for First Nations and Inuit people in Canada
LU: Limited use
Online access to formularies
BC: www.healthservices.gov.bc.ca/pharme/formulary/index.html
AB: www.ab.bluecross.ca/dbl/idbl_main1.html
SK: http://formulary.drugplan.health.gov.sk.ca
MB: www.gov.mb.ca/health/mdbif/index.html
ON: www.health.gov.on.ca/english/providers/program/drugs/odbf_
eformulary.html
QC: www.ramq.gouv.qc.ca/en/regie/lois/liste_med.shtml
8
osteoporosis update
Winter 2008
NB: www.gnb.ca/0051/0212/index-e.asp
NS: www.gov.ns.ca/health/Pharmacare/formulary.asp
PEI: www.gov.pe.ca/infopei/index.php3?number=45156
NL: www.health.gov.nl.ca/health/nlpdp/#Formulary
YT: www.hss.gov.yk.ca/publications
NIHB: http://www.hlthss.gov.nt.ca/Features/Programs_and_
Services/health_care/pdf/drug_benefit_list.pdf
p erspective
Lindy Fraser Memorial Award 2007
O
I
steoporosis Canada is pleased to announce that its
Scientific Advisory Council (SAC) has selected
Dr. Anthony Hodsman to receive this year’s
Lindy Fraser Memorial Award, in recognition of his valuable contribution to osteoporosis research and education.
This award was established in 1993 in honour of the
founder of the first osteoporosis support group in the world.
Dr. Hodsman has provided outstanding leadership
both as Chair of the SAC from 2003 to June 2006 and
through his significant research over the years, particularly in the area of parathyroid hormone (PTH) as a new
approach to osteoporosis therapy.
Trained in both endocrinology and nephrology,
Dr. Hodsman is currently Professor in the Department of
Medicine at the University of Western Ontario. He founded
the London Regional Osteoporosis Program in 1981 and
acted as Medical Director un­­til 2004. Dr. Hodsman’s
research interests lie mainly in the field of metabolic
bone disease, renal osteodystrophy and osteoporosis.
He has published extensively in the basic science and
clinical fields as well as on the application of clinical
practice guidelines in osteoporosis.
Upon receiving the award, Dr. Hodsman had this
advice for new researchers:
“First, I’d encourage young researchers to realize that
most of what we think we know about the skeleton is not
biologically correct. Therefore there are an infinite variety
of windmills to go and tilt at, with opportunities to get
closer to the truth. However, the real truth won’t be clear
until after retirement, so you’ll never run out of things to do.
“Second, pick a project that is sufficiently circumscribed
so that there is a good chance to become an expert — for
that, most people need either a mentor, or very good luck.
“Third, demand the time protection to accomplish
the goal. It is never worth being successful in a university
career at the expense of one’s family, health and friends.
It is necessary to visit Peru, or the Himalayas along the way.”
Please join Osteoporosis Canada and the SAC in
congratulating and thanking Dr. Anthony Hodsman.
Canada at ASBMR
TI
he American Society for Bone and Mineral Research
(ASBMR) 29th Annual Meeting was held in
Honolulu, Hawaii in September 2007, and featured
much important Canadian research. Here are some of
the highlights.
Long-terms effects of vitamin K
The long-term effects and safety of vitamin K, promoted
as a supplement for decreasing bone loss in postmenopausal
women, are unknown. ECKO (Evaluation of the Clinical
Use of Vitamin K Supplementation in Post-Menopausal
Women With Osteopenia), a 2-year placebo-controlled
double-blind trial, randomized 217 postmenopausal
women with osteopenia to receive 5 mg vitamin K1 daily
and 223 to placebo. Endpoints included bone mineral
density (BMD), bone turnover markers, fractures,
long-term side effects and health-related quality of life
(HRQOL). The study was extended for earlier participants for up to 4 years. Daily vitamin K supplements for
2 to 4 years did not protect against age-related decline in
osteoporosis update
Winter 2008
9
BMD in the study population, although it was associated
with lower incidences of clinical fractures and cancer.
HRQOL was not significantly different between the
2 groups. The team concluded that further studies are
needed to confirm the findings.
Cheung AM, Tile LE, Lee Y et al. Abstract M399
Case manager interventions
A randomized controlled trial by Morrish et al was
designed to determine the cost and effectiveness of
using case managers to improve inappropriately low
osteoporosis diagnosis and treatment rates in patients
who have undergone hip fractures. Patients recruited
from all hospitals in Capital Health, Edmonton (criteria
included age over 50 years, not on active osteoporosis
therapy except calcium/vitamin D and not in long-term
care) were randomized to intervention by a case manager
(n = 110) or usual care (n = 110). Case managers
arranged BMD testing, prescribed bisphosphonates
and communicated with primary care physicians. At
6 months, patients in the intervention group were more
likely to receive appropriate care (prescribed bisphosphonate therapy for T-score < –1.5) than controls
(67% vs 26%, adjusted p < 0.001), at a cost of $52 per
patient. The researchers concluded that case managers
provide a cost-effective way of substantially increasing
rates of testing and treatment for osteoporosis in hip
fracture patients.
Morrish DW, Majumdar SR, Beaupre LA et al. Abstract T329
Alendronate in cystic fibrosis patients
In the only Canadian randomized controlled trial of
bisphosphonates in adults with cystic fibrosis,
Papaioannou et al showed that alendronate was well
tolerated and increased BMD significantly over 12
months, compared with placebo. The multicentre trial,
which focussed on BMD changes, assigned 56 patients,
mean age 29.1, to either placebo or alendronate 70 mg
once-weekly for 12 months. Patients received daily
calcium and vitamin D supplements. The treatment
group had a 4.99% (95% CI: 2.40, 7.59) greater
increase in lumbar spine BMD and a 3.50% (95% CI:
1.37, 5.63) greater increase in proximal femur BMD
compared with the placebo group (adjusted for age,
BMI, baseline BMD, number of baseline vertebral
fractures).
Papaioannou A, Kennedy CC, Ionnidis G et al. Abstract W360
Adherence improves fracture rates
A population-based study by Jaglal et al confirms pre­
vious reports and should encourage continued efforts
to mon­itor treatment and improve adherence as an
ef­­fective means to reduce fracture rates. The researchers
looked at prescription refill compliance in 74,085
Ontario residents aged 67 and over who started an
osteoporosis medication between 2002–2004, after no
10
osteoporosis update
Winter 2008
prior bisphosphonate or SERM claim for 2 years.
Refill compliance was calculated using the Medication
Possession Ratio, defined as the number of days supplied from first to last prescription/length of follow-up
(730 days), at cut-offs of 30%, 50%, 67% and 80%.
In the period after the initiation of medication, there
were 1,751 (2.4%) fractures. Logistic regression analyses
were conducted for each refill compliance cut-off
(adjusted for age, sex, BMD, other medications,
number of physician visits in the 2-year period prior to
starting treatment, BMD after initiation of treatment,
and Charlson Comorbidity Index). Only 80% and
67% refill compliance were statistically significantly
associated with fracture reduction.
These data suggest that adherence of at least 67%
to 80% is required to effect a measurable reduction in
osteoporotic fractures.
Jaglal S, Thiruchelvam D, Hawker G. Abstract 1275
Validation of 10-year fracture risk prediction
Absolute 10-year fracture risk is the preferred method
for fracture risk assessment, but the validity of applying
published rates from one population to another is
uncertain. In this study that compared predicted and
observed fracture risk, Leslie et al concluded that
Swedish 10-year fracture risk data (used to predict risk
from age-only and age+BMD in Manitoba women age
47.5 years or older at the time of baseline femoral neck
BMD) are generally applicable to the Canadian female
population referred for BMD testing. Higher observed
vs estimated fracture rates for women age 77.5 years or
older may be explained by healthy selection bias (elderly
women referred for BMD testing have lower mortality
than expected, thus more years at risk for fracture).
Leslie WD, Tsang JF, Lix LM. Abstract 1078
Nitrates and BMD
Using data from the population-based Canadian
Multicentre Osteoporosis Study (Camos), researchers
demonstrated that nitrate use is associated with increased
BMD in men and women aged 50 years and older.
BMD was measured in 1,449 men and 2,682 women;
of these, 14 men and 35 women reported nitrate use.
Nitrate users were significantly older and weighed less
than nonusers. Both women and men users had lower
annual loss of BMD at all measured sites (hip, femoral
neck and lumbar spine) compared to nonusers. These
findings are con­sistent with earlier studies and reinforce
the need for a randomized trial to determine the relationship between nitrate use and fracture.
Jamal SA, Goltzman D, Hanley DA et al. Abstract 1266
For more information and to view more abstracts, please
visit the ABSMR website: www.asbmr.org. Montreal,
Québec will host the next annual meeting from September
12–16, 2008. ●
It’s the only bone formation
agent available in Canada.
Will
antiresorptive
therapy be enough?
Is it time to
stimulate new bone
with FORTEO?
FORTEO
can stimulate
new bone
formation.
RECOMMEND FORTEO for postmenopausal
women with severe osteoporosis.
RAPID increase in bone formation markers.*
REDUCED RISK of fracture has been
demonstrated.
* Daily administration of FORTEO to postmenopausal
women with osteoporosis stimulated bone formation. Peak
concentrations of procollagen I carboxy-terminal propeptide
(PICP) approximately 41% above baseline were observed after
1 month of treatment, followed by a decline to near-baseline
values by 12 months. Serum bone-specific alkaline phosphatase
(BSAP) concentration increased by 1 month of treatment and
continued to rise more slowly from 6 to 12 months; maximum
increases were 45% above baseline.
Teriparatide significantly reduced the incidence and severity of back pain. In women with
postmenopausal osteoporosis, there was a 26% reduction (p = 0.017) in the spontaneous reports
of new or worsened back pain compared to placebo.
FORTEO (teriparatide [rDNA origin] injection) is indicated for the treatment of
postmenopausal women with severe osteoporosis who are at high risk of fracture or
who have failed or are intolerant to previous osteoporosis therapy; and to increase
bone mass in men with primary or hypogonadal severe osteoporosis who have failed
or are intolerant to previous osteoporosis therapy. The effects of FORTEO on risk for
fracture in men have not been demonstrated.
severe renal impairment; metabolic bone diseases other than primary osteoporosis
(including hyperparathyroidism and Paget’s disease of the bone); unexplained
elevations of alkaline phosphatase; prior external beam or implant radiation therapy
involving the skeleton; bone metastases or a history of skeletal malignancies.
The safety and efficacy of FORTEO (teriparatide [rDNA origin] injection) have not
been evaluated beyond 2 years (median 19 months in women and 10 months in
men). Consequently, the maximum lifetime exposure to FORTEO for an individual
patient is 18 months. FORTEO should not be administered to women who are
pregnant or breastfeeding, nor to children or young growing adults. The safety and
efficacy of FORTEO have not been studied in pediatric populations. FORTEO is not
indicated for use in pediatric patients.
Physicians should become familiar with the full content of the Product
Monograph prior to prescribing FORTEO (teriparatide [rDNA origin]
injection). FORTEO should be prescribed only to patients for whom the
potential benefits outweigh the potential risk. In rats, teriparatide caused an
increase in the incidence of osteosarcoma that was dose- and treatment
duration-dependent at systemic exposures ranging from 3 to 60 times the
exposure in humans given a 20 mcg dose. FORTEO should not be prescribed
to patients who are at increased baseline risk for osteosarcoma.
FORTEO (teriparatide [rDNA origin] injection) is contraindicated in patients with
hypersensitivity to teriparatide or any of its excipients; preexisting hypercalcemia;
Adverse events considered to be related to FORTEO therapy were nausea, dizziness,
and leg cramps.
REFERENCE: FORTEO (teriparatide [rDNA origin] injection) Product
Monograph. Eli Lilly Canada Inc. June 3, 2004.
Patient support available at 1.877.4FORTEO
® Registered trademark owned by Eli Lilly and Company; used under license.
© 2007 Eli Lilly Canada Inc. Toronto, Ontario M1N 2E8.
www.lilly.ca
FTCAD01300807
prescribing summary
summaryenclosed
on page
See prescribing
about
Osteoporosis
Canada
Canadian Endocrine Update 2008
Osteoporosis Canada is a
national, not-for-profit
organization dedicated to
educating, empowering and
supporting individuals and
communities in the prevention
and treatment of osteoporosis.
The organization, guided by
its Scientific Advisory Council
(SAC) made up of osteoporosis
experts from across the
country, works with healthcare
professionals to make the
latest prevention, diagnostic
and treatment options available
to Canadians.
Save the date for an exciting 3-day symposium presented
by McMaster University and the University of Western Ontario,
in partnership with the Canadian Society of Endocrinology
and Metabolism (CSEM), American Association Of Clinical
Endocrinologists (AACE), Osteoporosis Canada (OC), Ontario
Association of Medical Radiology Technicians (OAMRT) and
International Society of Clinical Densitometry (ISCD).
Advances in Endocrinology and Metabolism will feature
state of the art lectures on common endocrine disorders,
diagnosis and man­agement, and will include an osteoporosis
symposium and ISCD course, jointly sponsored by OC, OAMRT and ISCD. Course Directors are Aliya Khan, MD,
FRCPC, FACP and Terri L. Paul, MSc, MD, FRCPC.
www.osteoporosis.ca
May 3 1 – Ju n e 1 , 2 0 0 8
St. Jo s e p h ’s H e a l t h c a re
Ham i l t o n , ON
For more information and registration details,
please visit the Health Professionals section,
Calendar of Events page, at www.osteoporosis.ca
ISCD Bone Densitometry Courses
For information and locations around the world,
contact Anabela Gomes at 860-586-7563;
[email protected]; www.ISCD.org