OSTEOPOROSIS MANAGEMENT IN RESPIRATORY

PATIENTS: AN EVIDENCE BASED APPROACH

Ganesh Subramanian, HBSc., MD; Tripti Papneja, MD; EA Yacyshyn, MD, FRCPC
University of Alberta, Department of Pulmonary Medicine and Rheumatology
Figure 3. Flow chart on Managing Bone Health in Patients Post-Lung Transplant
OBJECTIVES Table 2: Randomized Controlled Trials in Adult Patients with Cystic
Fibrosis Using Bisphosphonates.
All patients awaiting lung transplant or post lung transplant
Authors Year of Number Inclusion Intervention Follow- Post-Tx Post-Tx Fracture Notes
•To address some of the major challenges that plague physicians when treating low Publication of BMD up BMD BMD Reductio
bone mineral density for respiratory patients using derived clinical scenarios. Patients Criteria period- Change Change in n
months in femur
•To develop a flow chart based on current evidence on how to best manage bone BMD measurement, Spine radiographs, Adequate Calcium/Vit D supplements, Promote weight bearing
lumbar neck/hip Exercises, Cessation of Smoking, Assess and treat for secondary causes of OP including hypogonadism
health for patients with cystic fibrosis (CF), post-lung transplant and chronic spine
glucocorticoid (GC) therapy. Aris et al 2004 48* T-score of Oral alendronate 12 4.9±3.0% 2.9±3.2% vs not
-1 or below 10 mg/daily vs vs. -0.7±4.7% , p significant Pre-lung Transplant Post-Lung Transplant
placebo -1.8±4.0%, = 0.003

INTRODUCTION Chapman et al.2009 22** T-score of IV 24

p ≤ 0.001
6·14 ± 1·86 4·23 ± 1·3 No fractures 27 of 63 T-Score ≤ -1
Use GC protocol,
if taking GC Oral/IV BP for 1 year*. Repeat BMD in 1 year.
-1.5 or zoledronate(Z) 2 vs. vs. in either Z infusions led to
•Therapeutic osteoporosis trials and treatment guidelines have focused mainly on below mg every 3 0·44 ± 0·10, –2·5 ± 1·41%, group flu-like and MSK
months for 2 P = 0·021 P side-effects (6
postmenopausal women. However, patient populations presenting with low bone years vs placebo = 0·0028 severe, 2 Treat with oral/IV BP Annual BMD Further BP Treatment* Considerations based on BMD
and other risk factors for low BMD and fall.
mineral density (BMD) in respiratory clinical practice is varied, with cases withdrawals).
Repeat BMD in one year, then every 2-3 years.
encompassing the spectrum of complexity. Haworth et al 2001 31* Z-score of IV 6 4.1% vs 1.7% vs Not given severe bone pain in
-2 or below pamidronate(P) -1.7%, -1.3%, p = 73% receiving P, *IV Etidronate has also been studied in this patient population with only 10 lung transplant patients.
•We identified several key practice challenges in the management of osteoporosis 30 mg q 3 months p=0.001 0.029 thus the study was *If oral/IV BP can’t be tolerated, use 0.25 µg of calcitriol twice daily by mouth while monitoring serum/urinary calcium levels.
with respiratory diseases including patients with cystic fibrosis(CF), post-lung vs placebo stopped
transplant and chronic GC therapy. prematurely. Table 4: Randomized Controlled Trials in Adult Patients on Chronic GC
•These patients present a special therapeutic challenge as few data exist to guide Papaioannou 2008
et al.
56* T-score of Oral alendronate 12
-1 or below 70 mg once
5.20 ±
3.67% vs -
2.14 ± 3.32%, not
vs - 1.3 significant
no differences in
quality of life or
therapy* for Prevention and Treatment of Low BMD
osteoporosis clinical care for them. weekly vs 0.08 ± ±2.70%, p < the number of Authors Year N Inclusion BMD F/U Intervention Post-Tx changes in Post-Tx Changes in Fracture reduction Notes
placebo 3.93%, p < 0.001 adverse events criteria lumbar BMD femur hip BMD
0.001 Cohen et al 1999 224 N/A 12 risedronate 5 mg 0.6 ± 0.5% vs 0.8 ± 0.7% vs -3.1 ± decrease in vertebral Prevention Study

METHODS or placebo daily -2.8 ± 0.5%; P <

0.001
0.7; p < 0.001. fracture (5.7% vs 17.3%;
P = 0.072).

*All participants received supplemental oral vitamin D(800 IU) and calcium daily (1000 mg). Eastell et 2000 120 N/A 97 daily 2.5 mg +1.4% vs –1.6% (p -1% vs -3.6% (not Not significant Prevention Study
al. weeks risedronate vs = 0.009). significant)
Data Sources: EMBASE, MEDLINE, Cochrane database of systematic reviews ** calcium carbonate 600 mg and vitamin D2 1000 IU each twice daily. Prednisolone 25 mg orally per day for 3 days starting on
placebo
the morning of the first infusion; repeated with subsequent infusions if a reaction to the first infusion was thought likely.
and controlled trials, and ACP Journal Club. Nijs et al. 2006 201 N/A 18 alendronate (10 2.1% vs -1.9% 1.4 % vs -2.0% Not significant Pt. with rheumatic
mg) vs P<0.001. p<0.001. disease only
Selection process and quality assessment: The articles were screened on title,
Figure 2. Flow chart on Managing Bone Health in CF Patients alfacalcidol (1
abstract and full-text. Selected studies scored using the Jadad score4. μg) daily
Reid et al. 2001 290 N/A 12 risedronate 5 2.9 (0.49%) vs 0.4 1.8% (0.46%) vs - vertebral fractures Prevention Study
Data extraction: Carried out by first reviewer and verified by a second reviewer CF patients ≥ 18 years of age or > 8 years with one risk factor (ideal body weight <90%, FEV1 <50% predicted, mg/day for 12 (0.4%), p < 0.05 0.3 (0.5%), p <0.01 reduction in the
(κ=0.84). glucocorticoids 5 mg/day for 90 days/year, delayed puberty, or a history of fractures/transplant. months versus
placebo
combined risedronate
treatment groups, vs
placebo (p= 0.042).
Table 1. Inclusion criteria for the selection of publications.
Reid et al. 2009 833 2 cohorts: GC 12 5 mg IV 4·06% [SE 0·28] vs 1.45% [SE 0.31] vs not significant For prevention group:
Participants Included CF patients, patients on oral GC therapy, or post-lung BMD Measurement, Adequate Calcium/Vit D/Vit K supplements, Maintaining BMI > 50 percentile, Encouraging
th
use < 3 months zoledronic acid 2·71% [SE 0·28], 0.39% [SE 0.30], LS 2·60% [0·45] vs
Weight Bearing Exercises, Cessation of Smoking and Endocrine referral if hypogonadism or GC > 3 versus 5 mg oral p=0·0001 p=0.005 0·64% [0·46],
transplant with outcome data available (changes in lumbar BMD months. risedronate p<0·0001)
with treatment).
Saag et al. 1998 477 N/A 48 alendronate (5 or 2.1 and 2.9%, in 1.2 % and 1.0 % in 5 Not significant Prevention Study
Type of study Comparative studies of bisphosphonates(BP), raloxifene, and weeks 10 mg/day) vs 5 and 10 mg of and 10 mg of
placebo alendronate groups alendronate
teriparatide therapy for prevention and treatment of low BMD vs -0.4 % groups vs - 1.2%
Z/T score ≥ -1 -1< Z/T score > -2 BMD every
2-4 years Z/T score ≤ -2
Year(s) of publication 1950 to November 2009 Saag et al. 2009 428 T score ≤ -2 36 teriparatide 20 11.0% 6.3% versus 3.4% Vertebral fractures: had taken
or ≤ -1 plus a μg/day or versus 5.3% for for femoral neck (P 1.7% versus 7.7%, P prednisone or its
prevalent low alendronate 10 lumbar spine (p < < 0.001) =0.007; nonvertebral equivalent at ≥5
trauma or mg/day for 36 0.001) fractures :7.5% versus mg/day for ≥3
Language English Repeat BMD every Spine radiographs;
oral bisphosphonate atraumatic months 7.0%, P = 0.843 months prior to
5 years if history of a fragility fracture, starting prolonged(≥ 3 months) GC fracture screening.
Exclusions Studies with Jadad score < 3, studies on inhaled /IV GC, (alendronate ) preferred
therapy, awaiting lung transplant, or significant bone loss
studies of fluoride therapy, studies of calcium, calcitriol, and (>3% in the lumbar spine or >5 to 6% in the proximal femur) Stoch et al. 2009 173 T-score < –2.5 12 alendronate 70 2.45% vs –0.57%, 0.75% vs –0.44% , p Not significant Treatment study
mg q weekly p ≤ 0.001 = 0.008
vitamin D therapies, studies of calcitonin or oral pamidronate or Annual BMD
IV clodronate/etidronate, studies on thiazide and salt restriction, *2.5-7.5 mg of prednisone or equivalent therapy initiating for at least 3
studies of growth and sex hormones including hormone months
replacement therapy, and studies on weight bearing exercises •For patients < 18 years of age, Z score should be used; Z and T-scores are nearly equivalent for patients between 18-30 years
were excluded. and T-scores should be used for ages over 30.
•If oral BP is not tolerated, use IV BP with pretreatment with prednisone.
Figure 3. Flow chart on Managing Bone Health in Patients on Chronic GC
therapy
Table 3: Randomized Controlled Trials Using Bisphosphonates for Patients starting or Continuing GC for ≥ 3 months (prednisone ≥ 5 mg or equivalent
CASES prevention of bone loss following Lung Transplant.
Case Number 1: A 19-yr-old male with CF has T-score of -1.4 in lumbar spine and – 1.2 in femur neck. Authors Year of n Inclusion Intervention Follow- Post-Tx Post-Tx Fracture Notes BMD measurement*, Spine radiographs, Adequate Calcium/Vit D supplements, weight bearing exercises,
His last FEV1 was 62% predicted. No history of fractures/transplant or prolonged GC therapy. Please refer to Publication BMD up BMD BMD Reductio Cessation of Smoking, treat for secondary causes of OP including hypogonadism/treat for hypercalciuria if indicated
Table 2 and Figure 1 for appropriate management. Criteria period Change in Change n
Case Number 2: A 64-year-old male received lung transplant a month ago for end stage chronic - lumbar in Femur
obstructive lung disease. His post-transplant BMD shows T-score -1.1 in lumbar spine and – 0.8 in femur neck. months spine neck/hip
Please refer to Table 3 and Figure 2 for appropriate management. Treat with oral/IV BP** if starting GC with plan for Treat with oral/IV BP** if T-score <-1 after 3 months of GC
≥ 3 months usage (prednisone ≥ 5 mg or equivalent); therapy (prednisone ≥ 5 mg or equivalent);
Case Number 3: A 43-year-old female on 12.5 mg of prednisone for pulmonary sarcoidosis. GC was Aris et al 2000 37* spine Pamidronate 30 mg24 8.8 ± 2.5% vs 8.2 ± 3.8% not CF patients only. Annual BMD Annual BMD
started eight months ago and patient has been on alendronate 70 mg/week in last six months. T10 wedge T-score of iv q 3 2.6 ± 3.2, vs significant
compression fracture is incidentally discovered. Please refer to Table 4 and Figure 2 for management. -3.0 months vs placebo p ≤ 0.015 0.3 ± 2.2%,
*FRAX assessment underestimates glucocorticoid associated fracture risk.
p ≤ 0.015
**Teriparatide Efficacy has only been shown in with patients with T score ≤ -2 or of ≤ -1 plus a prevalent low trauma or
REFERENCES Braith et al. 2007 30* none Alendronate(A) 10 8
mg/d or
alendronate 10
1.4 ± 1.1% in Not given
alendronate
group vs -14.1
Not given A + RT showed a
greater increased
lumbar BMD,
atraumatic fracture. Calcitonin has been studied in this patient population but efficacy is not well-established.

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mg/d plus
resistance training
(A+RT)
± 3.9% in
placebo
10.8 ± 2.3% post
Tx. CONCLUSION
*All participants received supplemental oral vitamin D(800 IU) and calcium daily (1000 mg). Patients with CF, chronic GC therapy and post-lung transplant present a special
8. Clin Infect Dis. 2007;45:883-893.
10. Lancet. 2007;369:1519-1527. therapeutic challenge as few data exist to guide osteoporosis clinical care for them.
This evidence based approach would be a useful tool for busy clinicians in
managing these complex patients with low BMD.