Osteoporosis Canada
Fall 2009 • vol. 13 no. 3
Ostéoporose Canada
osteoporosis
update
Of kidney stones
and bone loss
Mechanisms and management
of nephrolithiasis-related
osteoporosis
case study
Canadian Publications Mail Sales Product Agreement No. 40063730
Minimizing fracture risk
in spinal cord injury patients
questions & answers
Is bicycling bad for bones?
Fracture and survival odds
in the elderly
resources & announcements
page 10
a practical guide
for Canadian physicians
editorial
osteoporosis
comment
update
Osteoporosis Update is published by
OSTEOPOROSIS CANADA
1090 Don Mills Road, Suite 301
Toronto, Ontario, M3C 3R6
Tel: (416) 696-2663 • Fax: (416) 696-2673
Toll Free: 1-800-463-6842
Osteoporosis in the light of
other medical conditions
I
Julie M. Foley, President & CEO
Dr. Famida Jiwa, Vice-President, Operations
Ania Basiukiewicz, Communications Manager
Parkhurst
400 McGill Street, 3rd Floor
Montréal, Québec, H2Y 2G1
Mairi MacKinnon, Managing Editor
Tel: (514) 397-8833 • Fax: (514) 397-0228
Email: [email protected]
Susan Usher, Corporate Editorial Director
Pierre Marc Pelletier, Senior Art Director
editorial board
Richard G. Crilly, MD, MRCP, FRCPC
University of Western Ontario
Sidney Feldman, MD, FCFP
University of Toronto
Abida Sophina Jamal, MD, PhD, FRCPC
University of Toronto
Heather McDonald-Blumer, MD, MSc, FRCPC
University of Toronto
Colleen Metge, BSc(Pharm), PhD
University of Manitoba
Suzanne Morin, MD, MSc, FRCP
McGill University
Anne-Marie Whelan, PharmD
Dalhousie University
©2009 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:
Merck Frosst Canada Ltd.
P&G Pharmaceuticals Canada and
sanofi-aventis Canada Inc.
The financial support received from sponsors
does not constitute an endorsement by
OsteopoRosis Canada of any of the
sponsors’ products or services.
ISSN 1480–3119
Canadian Publications Mail Sales Product
Agreement No. 40063730
Heather McDonaldBlumer, MD, MSc, FRCPC,
is Program Director
for Postgraduate
Rheumatology at the
University of Toronto
and Associate Director
of the Osteoporosis
Program at the
University Health
Network, in Toronto.
n this issue of Osteoporosis Update, we are privileged to hear from
experts on two specialized topics of great interest to health professionals involved in the care of individuals with osteoporosis.
In the feature article, Dr. Ramsey Sabbagh, a Québec nephrologist
and Adjunct Professor of Medicine at the McGill University Health
Centre, informs us regarding the significant link between nephrolithiasis — a relatively common condition in the general population
— and bone mineral density. This is an important topic, but not
always well understood. Questions arise such as: Should patients
with renal stones limit their calcium consumption? Are vitamin D
supplements safe? What are the appropriate dosages of calcium and
vitamin D? What therapies are effective in minimizing bone loss in
people with this condition? In his well-written and clear presentation,
Dr. Sabbagh provides some helpful diagnostic and management
points to guide clinicians.
The case study by Dr. Cathy Craven, Clinician Scientist/Physiatrist
in Toronto Rehab’s Spinal Cord Rehabilitation Program, deals with
sublesional osteoporosis (SLOP), a disease unique to people who
have sustained spinal cord injuries. Sublesional osteoporosis is
characterized by excessive bone resorption, deterioration in lower
extremity BMD and increased propensity for distal femur and proximal tibia fractures. There are currently no guidelines on treating
SLOP subsequent to spinal cord injuries. Dr. Craven’s informative
discussion of issues related to osteoporosis management in these
patients will help to increase awareness of the debilitating effect of
fractures on their functional ability and quality of life.
Also in this issue: George Ioannidis, a research methodologist from
McMaster University, addresses the relationship between fractures
and mortality and outlines steps to help improve outcomes in elderly
patients; and Panagiota Klentrou, Professor and Chair in the Department of Physical Education & Kinesiology at Brock University and a
member of the Osteoporosis Canada’s Scientific Advisory Council,
looks at the timely question of bicycling — and other intense sports
activities — and bone health. Finally, we have the pleasure of mentioning recent awards extended to some upcoming young researchers
in the osteoporosis community.
We welcome your comments and questions. Please address
correspondence to [email protected].
Return undeliverable Canadian addresses to:
Circulation, 400 McGill Street, 3rd Floor
Montréal, Québec H2Y 2G1
osteoporosis update
Fall 2009
2
a
case
stu dy
Issues in osteoporosis management
related to spinal cord injury
A
35-year-old male sustained T4 paraplegia secondary to a motor vehicle
accident two years ago, and is now wheelchair bound. Is osteoporosis
screening indicated? Does he require treatment? Are there any special
treatment considerations?
Cathy Craven, BA, MSc,
MD, FRCP(C), Assistant
Professor in the Department of Medicine,
Division of Physiatry
at the University of
Toronto, is a Clinician
Scientist/Physiatrist
and Manager of the
Bone Density Lab in
Toronto Rehab’s Spinal
Cord Rehabilitation
Program.
Spinal cord injury (SCI) results in diverse motor, sensory
and autonomic impairments that are determined by the
location and severity of the injury within the neural canal.
“Tetraplegia” describes lesions of the cervical spinal cord,
while “paraplegia” refers to thoracic cord lesions. A “complete
injury” is defined as the absence of any motor or sensory
function below the level of injury, including the sacral
segments, and “incomplete injury” by preservation of motor
or sensory function below the level of injury, including
sacral sparing.1 Of an estimated 900–1000 Canadians
who sustain a SCI each year, 80% are male,2 and 84% of
injuries occur in people under age 34.3 The most common
causes of SCI in Canada are motor vehicle accidents, falls,
diving and sports accidents and other medical conditions.2
The trend of increased survival in the first 2 years post SCI
and extended life expectancy has resulted in a shift in the
emphasis of healthcare provision from assuring survival
to minimizing secondary complications (including osteoporosis and fragility fracture) and enhancing quality of life.
Unique osteoporosis issues
Sublesional osteoporosis (SLOP) is a disease process unique
to people with SCI. SLOP is characterized by excessive
bone resorption, deterioration in lower extremity bone
mineral density (BMD) and bone architecture, and an
increased propensity for lower extremity fragility fracture.
SLOP is distinct from osteoporosis due to aging in its rapid
rate of onset, severity of BMD decline, skeletal distribution,
Table 1
Definition of sublesional osteoporosis (SLOP)
Age range
Definition
Men ≥ 60 years or postmenopausal women Hip or knee region T-score ≤ –2.5
Men ≤ 59 years or premenopausal women Hip or knee region Z-score < –2.0 with ≥ 3 risk factors for fracture
Men or women age 16–90
Prior fragility fracture and no
identifiable etiology of osteoporosis other than SCI
Note: T-score is the number of standard deviations BMD is above or below gender-specific young adult
mean peak bone mass. Z-score is the number of standard deviations BMD is above or below that expected for individuals of the same age and gender.
Adapted from Top Spinal Cord Inj Rehabil 2009;14(4):1-22.
3
osteoporosis update
Fall 2009
bone micro-architecture involvement, etiology and associated regional fracture risk.4-7 Among patients with motor
complete SCI, there is a 3% to 4% per month BMD decline
at the hip and knee. Typically, BMD of the hips, distal femur
and proximal tibia are 28%, 37%–43%, and 36%–50%
below that of age-matched peers at 12–18 months post
injury.8-13 There is disagreement whether this BMD decline
continues or stabilizes at some point after injury.5,7,9,14,15
Distal femur and proximal tibia fractures prevail;
25% to 46% of chronic SCI patients develop fragility
fractures, frequently caused by torsional stresses on the legs
during a transfer or compressive forces at the knee during
a low-velocity fall from a wheelchair.16-18 A single fragility
fracture often leads to a cascade of events that increase
patients’ morbidity due to complications of fracture
treatment and immobilization (e.g. heel or ankle ulcer
from a cast or deep venous thrombosis) and decrease their
functional abilities (i.e. immobilization devices or increased
need for attendant care services during healing). Fragility
fractures after SCI frequently result in delayed union, nonunion or mal-union, and amputation in extreme cases.17
Diagnosis and fracture risk assessment
Identification of patients with SLOP and high fracture risk
entails BMD testing and a review of fracture risk factors.
There are several established methods for measuring knee
region BMD.5,6,11,19-21 Regardless which is chosen, assessment of knee region BMD is crucial as it is the best predictor of knee fracture risk after SCI.22,23 Risk factors for
fragility fracture after SCI include: SCI before age 16,
paraplegia vs tetraplegia, complete vs incomplete SCI,
female vs male gender, duration of SCI > 10 years, BMI
≤ 25 kg/m2, knee region BMD below the fracture threshold,
an alcohol intake of > 5 servings per day, prior history of
fracture and maternal history of fracture.23-25
Lazo has shown that BMD T-scores are predictive of
risk fracture in men with SCI, noting a 2.8 times relative
increased risk of fracture for every one standard deviation
decrease in femoral neck T-score.26 Conventional measures of spine and hip region BMD in patients with SCI
are often inaccurate or difficult to interpret longitudinally
due to the presence of hardware, laminectomy, posterior
element degenerative changes at the spine and/or heterotopic ossification (abnormal formation of true bone within
extraskeletal soft tissues), contracture or dislocation at
the hip.27,28 Based on hip or knee BMD results (Table 1),
clinicians may identify patients with SLOP according to
their gender and age at the time of the scan.
Not all causes of low BMD after SCI are attributable
to SLOP; routine serum and urine screening among
patients with SCI identifies other contributing factors 30%
of the time: hyperthyroidism, vitamin D deficiency and
secondary hyperparathyroidism, renal insufficiency; alcoholism, hypogonadism (men) and amenorrhea (women).29
Treatment strategies
To date, no SLOP treatment trial has been adequately
powered to address fracture reduction among patients
with SCI. Most osteoporosis intervention trials have
selected increases in lower extremity BMD as a proxy for
fracture reduction. Treatments for SLOP after SCI include:
rehabilitation interventions, oral bisphosphonates, calcium
and/or vitamin D supplements and lifestyle modifications
(weight-bearing exercise, smoking cessation, counselling
on restriction of alcohol and caffeine intake). Prior to
initiating therapy, an assessment of the patient’s diet is
necessary to ensure sufficient — but not excessive —
calcium and vitamin D intakes. Excess calcium (above
1500–1750 mg/day) may precipitate bladder or kidney
stones, while too much vitamin D may lead to heterotopic
ossification among SCI patients. At Toronto Rehab, we
routinely recommend daily intakes of 1000 mg calcium
and 1000 IU vitamin D3 for patients with SCI.29
Recent systematic reviews summarize drug and rehabilitation interventions for SLOP treatment.30,31 Of the
17 studies reviewed (3 drug and 14 rehab), no intervention
led to sustained increases in hip or knee region BMD in
subjects with chronic SCI and SLOP. FES (Functional
Electrical Stimulation) cycle ergometry or passive standing
may be offered provided patients understand that these
are lifetime prescriptions, as the therapeutic benefit abates
with cessation of therapy.
Level 1b evidence supports alendronate for treatment
of patients with motor complete paraplegia. Using a randomized open-label design, Zehnder et al evaluated the
effectiveness of alendronate 10 mg daily and elemental
calcium 500 mg daily vs elemental calcium 500 mg daily
(alone) for 24 months. The study cohort consisted of 55
men with motor complete SCI. Injury duration ranged
from 1 month to 29 years post SCI, with group means
of 10 years post injury. The key findings included an
8.0% decline in tibia epiphysis BMD (the primary outcome) in the control group and relative maintenance of
tibia epiphysis BMD (–2.0%) in the treatment group
(p < 0.001). Patients with SLOP and motor complete
injury may be treated with alendronate (70 mg weekly) and
calcium (1000 mg daily in divided doses) and vitamin D
supplements, to ensure serum values in the therapeutic
range (75–150 nmol/L).32
Although many oral and intravenous bisphosphonates
are available on the market, only alendronate has been
shown to maintain hip and knee region BMD after SCI,
although fracture outcome studies have not been done.
There are no clinical trials evaluating drug treatments
of SLOP among patients with motor incomplete injuries.
Recent p-QCT data describing longitudinal changes in
lower extremity cortical and trabecular BMD over time
suggest there is a therapeutic window 2 to 8 years post
injury during which antiresorptive therapies are most likely
to be effective.33 Oral aminobisphosphonates should be
used with caution in patients with spinal cord lesions at or
above T6, as esophageal dysmotility is common after SCI
and the risk of esophageal erosions is increased compared
to individuals without SCI.34 Alendronate may also elicit
atrial fibrillation among patients with SCI and a propensity
for autonomic dysfunction. The propensity for arrhythmia
is specific to patients with SCI and lesions above T6.
Initiation of SLOP therapy necessitates repeat BMD
testing to evaluate effectiveness. Follow-up testing is
typically done every 1 to 2 years at the same facility, using
the same acquisition and analysis protocols. An increase
in BMD above the least significant change (LSC) suggests
effective therapy, while a decrease of greater than the
LSC prompts re-evaluation of the treatment protocol
and of patient adherence.
Increased survival and life expectancy
post SCI have shifted the emphasis to
minimizing complications, including
osteoporosis and fragility fracture
Increasing awareness of bone risks
In the absence of guidelines for the diagnosis and treatment of SLOP in people suffering from spinal cord injury,
clinicians should be aware of the important risk of fractures, especially of the lower extremities, which lead to
significant complications and declines in functional ability.
As in the case described above, men with paraplegia
warrant BMD and fracture risk screening. The patient
should undergo nutritional assessment to ensure a balanced diet, including appropriate amounts of calcium
and vitamin D, and should be counselled on the role of
rehab interventions (FES and passive standing) and lifestyle modifications to augment his bone mass. Pharmacologic therapy should be considered to maintain BMD
of the hip and knee regions. Given recent worries about
the spontaneous, atypical femoral fractures in non-SCI
patients who have been on alendronate for some years, a
maximum of 10 to 13 years of therapy is recommended.
This recommendation is speculative in nature, as these
patients are particularly susceptible to similar lower limb
fractures.35,36 ●
References
1. American Spinal Injury Association: Reference Manual for the
International Standards for Neurological and Functional
Classification of Spinal Cord Injury. Chicago, Illinois: ASIA, 1994.
2. Canadian Paraplegic Association. www.canparaplegic.org.
3. Rick Hansen Foundation. www.rickhansen.com.
4. Dauty M et al. Bone 2000;27(2):305-9.
Continued on page 9
osteoporosis update
Fall 2009
4
f eatu re
Bones and stones
The link between osteoporosis and nephrolithiasis
By Ramsey Sabbagh, MD, FRCPC
N
I
ephrolithiasis (kidney stone disease) is relatively
common in the general population, with a lifetime
incidence of approximately 12% in men and 6%
in women.1 Once affected by a kidney stone, an individual’s risk of having a recurrent episode can be higher than
50% over the next 10 years.2 Over 80% of all kidney stones
are calcium (most commonly calcium oxalate)-based.3
There are several potential risk factors for kidney stone
formation, including dietary/lifestyle considerations,
metabolic abnormalities and genetic susceptibility, and
approximately half of all calcium-containing stone formers are found to have hypercalciuria.3 Clinically, hypercalciuria is defined as a daily urine calcium excretion
exceeding 6.25 mmol in women or 7.5 mmol in men
(or > 0.1 mmol/kg/day in either women or men), in two
consecutive 24-hour urine collections.4 If serum calcium
is normal and secondary causes (Table 1) such as primary
hyperparathyroidism have been ruled out, hypercalciuria
is defined as “idiopathic” or “primary.” Indeed, the
majority of hypercalciuric calcium stone formers have
idiopathic hypercalciuria (IH).
A classification scheme for hypercalciuria developed
over 30 years ago5 divided the condition into absorptive,
resorptive and renal subtypes. Diagnosis was based on
urine sample results following an overnight fast, a low
calcium diet and an oral calcium load. However, categorizing patients using such a method is difficult in the
clinical setting and does not alter potential therapeutic
interventions. It is now thought that IH in most patients
may involve a complex combination of absorptive, resorptive and renal mechanisms: increased intestinal calcium
absorption, excessive calcium release from bone and abnormal renal calcium handling, respectively. This is supported
by evidence of bone mineral loss among individuals classified as absorptive hypercalciuric, even though such
patients have an increase in intestinal calcium absorption.6
Kidney stones and bone mineral loss
Ramsey Sabbagh, MD,
FRCPC, is a nephrologist
at the Centre hospitalier
Pierre-Le Gardeur and
Centre hospitalier régional
de Lanaudière, and
Adjunct Professor of
Medicine at the McGill
University Health Centre
(MUHC) in Montreal,
Québec.
5
The relationship between renal stones, specifically hypercalciuric nephrolithiasis, and bone mineral density (BMD)
is well established. A large epidemiologic study evaluating
factors associated with BMD in men showed that a history of renal stones was associated with lower BMD.7
In addition, population-based studies have shown an
increased fracture risk among participants with a kidney
stone history. This relationship was stronger among males;8,9
nevertheless, hypercalciuria plays an important role in
osteoporosis among postmenopausal women, with a
osteoporosis update
Fall 2009
prevalence as high as 19% in those referred to a metabolic bone disease clinic.10 Indeed, menopause is associated with an increase in renal calcium excretion, but a
large epidemiologic study showed a correlation only
between surgical menopause and incident kidney stones.11
Genetic and dietary factors
Several potential mechanisms linking BMD loss and IH
have been proposed. Approximately half of all patients
with IH have a family history of nephrolithiasis. Even
though genetic factors may have a significant effect on
both BMD and hypercalciuria, a common genetic variant linking most cases of IH and BMD loss has yet to be
discovered. Common genetic variations have been found,
however, in small subsets of patients with renal stones
and BMD loss. For example, Prié et al described cases of
nephrolithiasis, bone demineralization and hypophosphatemia (low serum phosphorus) associated with a
mutant type 2a sodium-phosphate cotransporter.12
Dietary factors that may link hypercalciuria with
BMD loss have revolved around the balance of calcium,
sodium and protein intake:
• In the past, patients with hypercalciuric nephrolithiasis
may have been advised to limit their calcium consumption, or done so independently, based on the
notion that it might help minimize further stone formation. This restriction can lead to a negative calcium
balance and has been associated with BMD loss. We
now know that calcium restriction may in fact heighten
the risk of new symptomatic renal stones in such
patients, by allowing for increased intestinal oxalate
absorption (and, as a result, greater urinary oxalate
excretion).13 Therefore, a normal dietary calcium
intake is essential in patients with IH and renal stones.
• While a high-sodium diet is not usually the sole cause
of hypercalciuria, it may aggravate this condition by
inducing volume expansion, reducing sodium transport
and, consequently, decreasing calcium reabsorption
in the proximal tubule. Increasing dietary sodium by
100 mEq will raise urinary calcium excretion by
approximately 0.6 mmol in a normal subject, but may
increase it by over 1 mmol in someone with IH.4 In
addition, Martini et al showed that a high salt intake
was predictive of low BMD in calcium stone formers
after multivariate adjustments, and reducing dietary
sodium may have a positive effect on bone metabolism.14
• A diet rich in animal protein is associated with hypercalciuria and stone disease. Bone buffering of the acid
A normal dietary calcium intake is essential in patients with idiopathic hypercalciuria
and renal stones. If supplements are needed, they should be taken with meals
load provided by animal protein causes calcium release
from bone, and the acid load may directly inhibit calcium reabsorption in the renal tubule.15 Acid derived
from animal protein may also reduce urinary excretion
of citrate, an inhibitor of stone formation. While some
research has supported a detrimental effect of an acid
load on bone, studies have been conflicting.16-18
Management
Dietary management
Patients with hypercalciuric nephrolithiasis should maintain
a diet with a sodium intake of less than 100 mEq (2.3 g)
per day and an animal protein intake of less than 1 g per kg
of body weight per day.
What about calcium supplements?
A common clinical dilemma involves the use of calcium
supplements in patients with osteoporosis who have a
history of renal stones. Results from large epidemiologic
studies have varied. In the Nurses’ Health Study I, supplementation was associated with a 1.2 relative risk of stone
formation,13 while other studies did not report an increased
risk.19,20 A reason for this discrepancy may be related to
the timing of calcium supplement ingestion and whether
or not the supplement is taken with a meal.21 When it is
taken without food, no intestinal oxalate is available to
bind with the calcium, leading to an increase in calcium
absorption and urinary excretion, without reduction of
daily oxalate absorption/excretion. It may be wise to
advise such patients to obtain most of their daily calcium
from food; if supplements are necessary (e.g. in the case
of lactose-intolerance), patients should be reminded to
take them with meals. Using a calcium citrate salt may
provide the added benefit of citrate in stone formers.22
The role of citrate
Citrate is a natural urinary inhibitor of calcium stone
formation, and hypocitraturia may contribute to renal
stone disease in some patients. Hypocitraturia may be
idiopathic or secondary to conditions associated with a
chronic metabolic acidosis, such as renal tubular acidosis
or chronic diarrhea. In addition, a high animal protein diet,
which generates a significant acid load, may also reduce
urinary citrate. Considering the effect of acid buffering
on bone mineral loss, some studies have investigated the
effect of citrate supplementation (an alkali equivalent) on
BMD in recurrent calcium stone formers, demonstrating
a mild benefit in lumbar spine and distal radius BMD.23,24
Is vitamin D supplementation safe?
Research is lacking on the isolated effect of vitamin D
supplements in calcium stone formers. Studies have demon-
strated that high doses of vitamin D are safe in non-stone
formers, with no significant effect on urinary calcium.25,26
Although usual vitamin D dosing of 400–800 IU/day for
osteoporosis patients is likely safe in stone formers, one
must keep in mind that some people with IH have elevated
1.25[OH]2 vitamin D levels associated with a “hypersensitive” 1α-hydroxylase enzyme (the kidney enzyme
responsible for converting the major circulating form of vitamin D, 25[OH]D3, to the active metabolite 1.25[OH]2D3).
Augmenting 25[OH] vitamin D with supplementation in
such patients may increase 1.25[OH]2 vitamin D, intestinal calcium absorption and urinary calcium excretion.4, 27
Therefore, it is advisable to monitor the urinary calcium
response in individuals who are calcium stone formers and
who are taking vitamin D supplements for bone health.
Thiazide diuretics
If a patient with reduced BMD is discovered to have hypercalciuria, secondary causes should be ruled out and dietary
parameters optimized. If the IH persists (i.e. daily urinary
calcium excretion in two consecutive collections > 6.25 mmol
in women or 7.5 mmol in men, or > 0.1 mmol/kg/day
in women or men), the mainstay of therapy is a thiazide
diuretic. Thiazides reduce urinary calcium excretion by
Table 1. Causes of secondary hypercalciuria
Dietary factors
• Excessive calcium intake
• Excessive salt intake (> 6 g/day)
• High animal protein intake
• Diet low in phosphates (chelators)
• Low potassium
Other causes
1. Increased intestinal absorption of calcium
• Overdose of vitamin D
• Increased production of 1.25[OH]2D3 due to primary hyperparathyroidism,
sarcoidosis and other granulomatous diseases (tuberculosis), lymphoma
• Severe hypophosphatemia (mesenchymal tumours, Fanconi syndrome)
2. Increased osteoclastic bone resorption
• Bone metastases, myeloma
• Primary hyperparathyroidism
• Flare of Paget’s disease
• Prolonged immobility (mainly in young subjects)
• Hyperthyroidism
3. Decreased reabsorption of calcium by the renal tubule
• Loop diuretics
• Medullary sponge kidney (dilatation of the terminal collecting tubules
producing a brush-like papillary blush or a “bouquet of flowers” image
on the intravenous urogram done to investigate nephrolithiasis)
• Glucocorticoid therapy, Cushing’s disease
• Renal tubule disorders responsible for hypercalciuria with nephrolithiasis
Adapted from Audran M, Legrand E. Hypercalciuria. Joint Bone Spine 2000;67:509-15.
osteoporosis update
Fall 2009
6
as much as 50%,28 and calcium stone recurrence by over
50%.29,30 Further, they have been associated with a beneficial effect on BMD and hip fracture risk.31-33 The typical
starting dose of hydrochlorothiazide is 25 mg daily, but it
is not uncommon to require at least 50 mg/day for adequate
urinary calcium reduction. A 24-hour urine collection
can be repeated after 6–8 weeks of therapy. If a reduction
below the hypercalciuric range defined above has not been
achieved, one should consider increasing the thiazide dose.
It is important to avoid diuretic-associated hypokalemia
(low serum potassium), which may induce hypocitraturia.
Some clinicians add a potassium-sparing diuretic, such
as amiloride, to thiazide therapy to avoid hypokalemia
and possibly further reduce calcium excretion in a synergistic manner.
Bisphosphonate therapy
Several studies have demonstrated a beneficial effect of
bisphosphonates on urinary calcium parameters and BMD
in people with IH.34,35 A recent randomized controlled trial
studied the effect of alendronate and indapamide (a thiaziderelated diuretic), alone or in combination, on 24-hour urine
calcium and BMD after one year of therapy in 77 hypercalciuric postmenopausal women with low BMD. The
authors concluded that combination therapy was superior
to alendronate alone with regards to minimizing urinary
calcium excretion and optimizing lumbar spine BMD.36 Key diagnostic and management points
A significant link exists between low BMD and nephrolithiasis. The following are some key points:
• Measurement of 24-hour urinary calcium excretion
is an important component of secondary bone loss
evaluation, since an abnormal result has specific therapeutic implications. IH is diagnosed when elevated
urinary calcium is found in at least two urine collections, under optimal dietary conditions, in a normocalcemic state, and when secondary causes of
hypercalciuria have been eliminated.
• High sodium and animal protein intakes may exacerbate
hypercalciuria and BMD loss, and should be avoided.
• IH patients should maintain a normal daily calcium
intake, with supplements (taken with meals) if needed.
Calcium citrate may be a preferable supplement form.
• Patients may benefit from a thiazide diuretic to
reduce their urinary calcium excretion. Care must be
taken to avoid diuretic-associated hypokalemia.
• Vitamin D supplementation is likely safe in IH when
given at usual doses for bone health, but there is little
research addressing this issue.
• The addition of a bisphosphonate may be appropriate in particular patients with high risk of fracture,
but further studies are required.
• Finally, individuals with IH and recurrent stone
formation may benefit from referral to a renal stone
specialist for a complete metabolic evaluation. ●
7
osteoporosis update
Fall 2009
References
1. Lieske JC et al. Renal stone epidemiology in Rochester, Minnesota:
an update. Kidney Int 2006;69(4):760-4.
2. Uribarri J et al. The first kidney stone. Ann Intern Med 1989;111:1006-9.
3. Coe FL et al. The pathogenesis and treatment of kidney stones.
N Engl J Med 1992;327(16):1141-52.
4. Audran M, Legrand E. Hypercalciuria. Joint Bone Spine 2000;67:509-15.
5. Pak CY et al. A simple test for the diagnosis of absorptive, resorptive
and renal hypercalciurias. N Engl J Med 1975;292(10):497-500.
6. Vezzoli G et al. Intestinal calcium absorption is associated with bone
mass in stone-forming women with idiopathic hypercalciuria. Am J
Kidney Dis 2003;42(6):1177-83.
7. Cauley JA et al. Factors associated with the lumbar spine and proximal
femur bone mineral density in older men. Osteoporos Int 2005;16:1525-37.
8. Melton LJ III et al. Fracture risk among patients with urolithiasis:
A population-based cohort study. Kidney Int 1998;53:459-64.
9. Lauderdale DS et al. Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition
Examination Survey. J Bone Miner Res 2001;16:1893-8.
10.Giannini S et al. Hypercalciuria is a common and important finding
in postmenopausal women with osteoporosis. Eur J Endocrinol 2003;
149:209-13.
11.Mattix Kramer HJ et al. Menopause and postmenopausal hormone use
and risk of incident kidney stones. J Am Soc Nephrol 2003;14:1272-7.
12.Prié D et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate
cotransporter. N Engl J Med 2002;347(13):983-91.
13.Curhan GC et al. Comparison of dietary calcium with supplemental
calcium and other nutrients as factors affecting the risk for kidney
stones in women. Ann Intern Med 1997;126(7):497-504.
14.Martini LA et al. High sodium chloride intake is associated with low
bone density in calcium stone-forming patients. Clin Nephrol
2000;54(2):85-93.
15.Houillier P et al. Calciuric response to an acute acid load in healthy
subjects and hypercalciuric calcium stone formers. Kidney Int 1996;
50:987-97.
16.Kerstetter JE et al. Dietary protein, calcium metabolism, and skeletal
homeostasis revisited. Am J Clin Nutr 2003;78(3 Suppl):584S-592S.
17.Hannan MT et al. Effect of dietary protein on bone loss in elderly
men and women: the Framingham Osteoporosis Study. J Bone
Miner Res 2000;15(12):2504-12.
18.Heaney RP, Layman DK. Amount and type of protein influences
bone health. Am J Clin Nutr 2008;87(5):1567S-1570S.
19.Curhan GC et al. Dietary factors and the risk of incident kidney
stones in younger women: Nurses’ Health Study II. Arch Intern Med
2004;164(8):885-91.
20.Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk
of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15(12):3225-32.
21.Domrongkitchaiporn S et al. Schedule of taking calcium supplement and the risk of nephrolithiasis. Kidney Int 2004;65(5):835-41.
22.Levine BS et al. Effect of calcium citrate supplementation on urinary
calcium oxalate saturation in female stone formers: implications for
prevention of osteoporosis. Am J Clin Nutr 1994;60(4):592-6.
23.Pak CY et al. Prevention of spinal bone loss by potassium citrate in
cases of calcium urolithiasis. J Urol 2002;168(1):31-4.
24.Vescini F et al. Long-term potassium citrate therapy and bone mineral
density in idiopathic calcium stone formers. J Endocrinol Invest 2005;
28(3):218-22.
25.Vieth R et al. Efficacy and safety of vitamin D3 intake exceeding the
lowest observed adverse effect level. Am J Clin Nutr 2001;73(2):288-94.
26.Kimball SM et al. Safety of vitamin D3 in adults with multiple
sclerosis. Am J Clin Nutr 2007;86(3):645-51.
27.Bataille P et al. Diet, vitamin D and vertebral mineral density in hypercalciuric calcium stone formers. Kidney Int 1991;39(6):1193-205.
28.Coe F et al. Kidney Stones: Medical and Surgical Management.
Philadelphia: Lippincott-Raven 1996, p. 779.
29.Laerum E, Larsen S. Thiazide prophylaxis of urolithiasis. A doubleblind study in general practice. Acta Med Scand 1984;215(4):383-9.
30.Ettinger B et al. Chlorthalidone reduces calcium oxalate calculous recurrence but magnesium hydroxide does not. J Urol 1988;139:679-84.
31.Wasnich RD et al. Thiazide effect on the mineral content of bone.
N Engl J Med 1983;309(6):344-7.
32.Morton DJ et al. Thiazides and bone mineral density in elderly men
and women. Am J Epidemiol 1994;139(11):1107-15.
33.Schoofs MW et al. Thiazide diuretics and the risk for hip fracture.
Ann Intern Med 2003;139(6):476-82.
34.Weisinger JR, Alonzo E, Machado C et al. Role of bones in the
physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate. Medicina (B Aires) 1997;57 Suppl 1:45-8.
35.Heilberg IP et al. Effect of etidronate treatment on bone mass of
male nephrolithiasis patients with idiopathic hypercalciuria and
osteopenia. Nephron 1998;79(4):430-7.
36.Giusti A et al. Alendronate and indapamide alone or in combination
in the management of hypercalciuria associated with osteoporosis: a
randomized controlled trial of two drugs and three treatments.
Nephrol Dial Transplant 2009;24(5):1472-7.
qu estions
&
answers
q.
What strategies should physicians adopt to help
improve outcomes after osteoporotic fractures,
including mortality, in elderly patients?
George Ioannidis, PhD, responds: Osteoporosisrelated fractures are a major health concern in Canada.
The consequences of fracture are serious, including death.
In a recent CaMos (Canadian Multicentre Osteoporosis
Study) study of 7783 community-dwelling women and
men aged 50 years and older, researchers found a 2.7 and
3.2 fold increase in death over a 5-year period in individuals
who developed a new spine or hip fracture, respectively
(CMAJ 2009;181[5]:265-71). Other fractures (e.g. wrist,
forearm, ribs) were not found to have an impact on mortality. Findings were adjusted for other factors that might
influence mortality, such as comorbid diseases, medications,
health-related habits (e.g. smoking, physical activity), education level and quality of life. In contrast to other studies
suggesting increased mortality for men after fractures, this
study did not find differences between men and women.
While a broken hip may not be a direct cause of death
in the early post-fracture phase, the resultant immobility
can be a trigger for life-threatening processes such as pneumonia, DVTs, etc. Moreover, it may lead to a progressive
decline in health due to lack of mobility and loss of muscle
mass and strength, in turn causing disability and other
negative health consequences, including eventual death.
Vertebral fracture was found to be an independent predictor of death. It may influence death directly by causing
chronic back pain, immobility and postural change, and
increased risk of infection.
These findings are a wake-up call for physicians to
carefully monitor individuals who are at risk or have had
an osteoporotic fracture. All postmenopausal women and
men over 50 years of age should be assessed for risk factors
for fracture. Those with major risk factors (prior fracture,
use of systemic glucocorticoid therapy, family history of
fracture, propensity to fall) and individuals over age 65
should have a bone mineral density (BMD) test. For people
at high risk, treatment should be initiated; in Canada,
we have access to therapies that can reduce the risk of new
fractures by approximately 50%, and some of these work
as early as within 6 months. Calcium and vitamin D are
important additions to pharmacologic interventions.
Steps should be taken to reduce the likelihood of falling
— a major cause of injury among older people. Physical
activity should be encouraged to improve strength, balance
George Ioannidis, PhD, is a health research methodologist at McMaster University
in Hamilton, Ontario.
Panagiota (Nota) Klentrou, PhD, is Professor and Chair in the Department of
Physical Education & Kinesiology at Brock University in St. Catharines, Ontario.
q.
and flexibility. Since poor vision may also contribute to
accidents and falls, regular eye exams should be performed
(Harwood RH et al. Br J Ophthalmol 2005; 89:53-9).
Patients need to take care to remove fall hazards around
the home: keep stairs and walkways uncluttered, secure or
remove rugs, and rearrange kitchens cupboards and closets
so that items are within easy reach. Finally, following a
fracture, appropriate rehabilitation efforts need to be
conducted to improve strength, range of motion and
mobility so that individuals can return home, instead of
to long-term care facilities.
Appropriate osteoporosis management should improve
patient health-related outcomes and, hopefully, reduce
the likelihood of death following a fracture. However,
further research is needed to determine the precise relationship between fracture rates and death.
Patients have asked about the effects of bicycling on
bone health. Should people at risk of osteoporosis or
fractures avoid this type of exercise?
Panagiota Klentrou, PhD, explains: Recent crosssectional studies have reported low bone mass in competitive
male cyclists (Medelli J et al. J Clin Densitom 2009;12:
28-34; Smathers AM et al. Med Sci Sports Exerc 2009;41:
290-6). A longitudinal study of a group of 27- to 44-year-old
male competitive cyclists followed for one year has also
found that BMD decreased significantly in the peripheral
regions, but not in the lumbar spine (Barry DW, Kohrt
WM. J Bone Miner Res 2008;23:484-91). On the other
hand, this is not necessarily unique to cycling — past
studies have shown that some endurance athletes have low
BMD, possibly related to low body weight and fat mass
(Hind K et al. Bone 2006;39:880-5). While of great
interest, these studies reflect a select group of competitive
athletes and may not apply to the general population.
Lending further confusion to this story is a study by a
group of British researchers who examined the link between
physical activity and self-reported incidence of fractures in
34,000 men and women, 20 to 89 years old, in the UK.
They found a significant increased risk of fractures associated with bicycling and a moderately increased risk related
to other sports. It was hypothesized that this was likely due
to a higher incidence of injury (Appleby PN et al. J Bone
Miner Metab 2008;26:191-8).
As always, the balance of the benefit of the activity vs
the risk that it may impart becomes key. There doesn’t
appear to be substantial data to indicate that casual bicycling would negatively impact bone health. However,
people who are at increased risk of fractures may want to
pick and choose their cycling activities carefully to help
minimize the risk of falls and potential injury. Since there
are a variety of exercises and activities recommended for
people with low BMD, taking intense cycling off the list
may have merit. ●
osteoporosis update
Fall 2009
8
p erspective
Lindy Fraser Memorial Award
T
he Lindy Fraser Memorial Award was created in
honour of an Ottawa woman who was among the
first in Canada to be treated with newer osteoporosis
therapies, and who, in 1981, went on to create the first
self-help group for others with this condition. Her voluntary efforts on behalf of her fellow citizens prepared the
ground for the development of Osteoporosis Canada.
It is with great pleasure that we announce the Lindy
Fraser Memorial Award winner for 2009 — Dr. Suzanne
Morin. Dr. Morin was nominated by her colleagues on
the Scientific Advisory Council (SAC) and is recognized
for her dedication to Osteoporosis Canada, where she
has served as a consultant since 2005.
Dr. Morin has served on the Osteoporosis Canada
Board and as Chair of the Board Development Committee, and is currently a member of the SAC Executive
Committee. She was a driving force
behind the establishment of Osteo­
porosis Canada’s Montreal Chapter,
and has been actively involved on their
executive as president. Dr. Morin is also
a tireless promoter and speaker at scientific and public forums.
Dr. Morin is Associate Professor in
the Department of Medicine at McGill
University, and Internal Medicine Clinic
Director at the Montreal General Hospital. Her
research interests include pharmacologic therapies and
health-related outcomes for osteoporosis, particularly
following hip fractures.
Kudos to Dr. Suzanne Morin from all of us at
Osteoporosis Canada!
Dr. Bill Leslie, SAC Chair,
presents the 2009 award
to Dr. Suzanne Morin
at the American Society
for Bone and Mineral
Research Annual Meeting
in September 2009.
OC–CaMos Fellowship Award
O
I
steoporosis Canada (OC) and the Canadian
Multicentre Osteoporosis Study (CaMos) have
recently formed a new partnership to provide a
one-year fellowship award of $20,000 for a graduate student or postdoctoral fellow to pursue research training
with CaMos investigators. By supporting bright young
minds, the award encourages advances in research aimed
at improving osteoporosis prevention, diagnosis and
management.
OC and CaMos chose the following recipients for the
2009 award from a strong group of applicants:
• Lisa-Ann Fraser, Department of Clinical Epidemiology
& Biostatistics, Health Research Methodology Program,
McMaster University; Research project — The study
of Canadian women who sustain a fragility fracture,
to determine if a care gap is present (CaMos Mentor,
Dr. Alexandra Papaioannou)
• Kyle Nishiyama, Department of Mechanical Engineering, University of Calgary; Research project —
In vivo quantification of cortical bone porosity by highresolution peripheral quantitative computer tomography
(CaMos Mentor, Dr. Steven Boyd)
Best wishes to Lisa-Ann Fraser and Kyle Nishiyama as well
as to all the candidates as they embark on their exciting
careers in the field of osteoporosis.
For more information, please visit www.camos.org. ●
Continued from page 4
5. Eser P et al. J Musculoskelet Neuronal Interact 2004;4(2):197-8.
6. Garland D et al. Contemp Orthoped 1993;26(4):375-9.
7. Garland DE et al. Top Spinal Cord Inj Rehabil 2005;11(1):48-60.
8. Biering-Sorensen F et al. Paraplegia 1988;26(1988):293-301.
9. Frey-Rindova P et al. Spinal Cord 2000;38:26-32.
10. Hangartner TN. Physical Medicine and Rehabilitation Clinics of
North America 1995;6(3):579-94.
11. Kiratli BJ et al. J Rehab Res Devel 2000;37(2):225-33.
12. Finsen V et al. Paraplegia 1992; 30(5): 343-7.
13. Chow YW et al. Spinal Cord 1996;34(12):736-41.
14. Bauman W et al. Osteoporos Int 1999(10):123-7.
15. Demirel G et al. Spinal Cord 1998;36(12):822-5.
16. Vestergaard P et al. Spinal Cord 1998;36(11):790-6.
17. Comarr AE et al. Top Spinal Cord Inj Rehabil 2005;11(1):1-10.
18. Freehafer AA. Arch Phys Med Rehabil 1995;76(9):823-7.
19. Morse LR et al. Arch Phys Med Rehabil 2009;90(5):827-31.
20. Shields RK et al. Arch Phys Med Rehabil 2005;86(10):1969-73.
21. de Bruin ED et al. Spinal Cord 2005; 43(2):96-101.
22. Eser P et al. Arch Phys Med Rehabil 2005;86(3):498-504.
9
osteoporosis update
Fall 2009
23. Garland DE et al. Top Spinal Cord Inj Rehabil 2005;11(1):61-69.
24. Parsons KC, Lammertse DP. Arch Phys Med Rehabil 1991;72(4S):
S293-294.
25. Morse LR et al. Osteoporos Int 2009;20(3):385-92.
26. Lazo MG et al. Spinal Cord 2001;39:208-14.
27. Bauman WA et al. Spinal Cord 2009;47(8):628-33.
28. Brown A et al. J Clin Densitom 2006;9(2):230.
29. Craven BC et al. Top Spinal Cord Inj Rehabil 2009;14(4):1-22.
30. Craven BC et al. In Eng J et al, eds. Spinal Cord Injury Rehabilitation
Evidence. Version 2.0. Vancouver: ICORD 2008;9.1-9.24.
31. Bryson JE, Gourlay M. J Spinal Cord Med 2009; 32(3):215-25.
32. Holick MF. N Engl J Med 2007;357(3):266-81.
33. Frotzler A et al. Bone 2008;43(3):549-55.
34. Gore R et al. Spine 1981;6:538-44.
35. Emkey R et al. J Bone Miner Res 2002;17:S139.
36. Ali, T, Jay RH. Age and Ageing 2009; 38(5):625-6.
Complete references are available upon request:
[email protected]
about
Osteoporosis
Canada
Osteoporosis Canada is a
national, not-for-profit
organization dedicated to
educating, empowering and
supporting individuals and
communities in the risk reduction
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.
www.osteoporosis.ca
International Society for
Clinical Densitometry (ISCD)
16 th Annual Meeting
Evolution of Skeletal Health
over the Bone and Joint Decade
March 10-13, 2010
Grand Hyatt San Antonio
San Antonio, Texas
Learn from leading authorities on topics including:
Diagnostic methodologies and skeletal health assessment
Reimbursement and related care management
Medication, nutrition and rehabilitation
Surgical management post fracture
Diagnostic and treatment guidelines related to skeletal disease
For more information and updates on the program,
please visit www.iscd.org/Visitors/conferences.
ISCD Bone Densitometry Courses
The ISCD offers courses for clinicians, technologists, scientists,
researchers and healthcare providers. For information and locations around the world, contact Anabela Gomes:
Tel: 860-586-7563 ext 583
Email: [email protected]; www.ISCD.org