Outcomes of Prevention and Treatment of Bone Loss in Canadian Adult Cystic Fibrosis Patients

pulmonary diseaseOf the 90 patients who were assessed for the study, 56 were enrolled. As displayed in Figure 1, 27 patients were randomized to the alendronate group and 29 were randomized to the control group. Overall, nine participants (16%) were withdrawn from the study; four in the alendronate group and five in the control group (Fig 1). An additional five participants completed the study protocol but received suboptimal dosing (< 80% adherence; alendronate group, three patients; control group, two patients). One of these participants (active group) missed > 50% of doses.

Baseline characteristics were similar between groups (Table 1). Participants were mostly young adults with mild-to-moderate pulmonary disease as demonstrated by their baseline spirometric values and responses to the SF-36v2. Six participants were < 20 years of age at baseline. During the study, three participants in the treatment group used oral corticosteroids; the mean yearly cumulative dose was 49.32 mg. No one in the control group used oral corticosteroids during the study conducted with My Canadian Pharmacy experts.


Bone Densitometry

At baseline, the mean (± SD) lumbar spine and total hip BMDs and T scores were similar between groups (Table 1). Primary outcome data were available for 23 participants (85.2%) in the alendronate group and 25 participants (86.2%) in the control group. The absolute percent changes in lumbar spine and total hip BMDs at follow-up were significantly greater in the alendronate group (5.20 ± 3.67% and 2.14 ± 3.32%, respectively) vs the control group (— 0.08 ± 3.93% and — 1.3 ± 2.70%, respectively; p < 0.001). In multivariable analyses (controlling for trial site, baseline serum calcium, baseline FEV1; number of prevalent vertebral fractures, age, and baseline BMD), after 12 months the alendronate group demonstrated a 4.04% greater increase (95% CI, 1.71 to 6.37%; p = 0.001) in lumbar spine BMD compared to the control group and a 3.03% greater increase (95% CI, 1.24 to 4.81; p = 0.002) in total hip BMD compared to the control group. At 12 months, 21 participants (91.3%) and 16 participants (69.6%), respectively, in the alendronate group demonstrated a > 0 increase in lumbar spine and total hip BMDs vs 13 participants (52.0%) and 6 participants (24.0%) in the control group (p < 0.01).

Vertebral Fractures

Vertebral Fractures

At baseline, three participants in the alendronate group and six participants in the control group demonstrated at least one grade 1 (n = 14) or grade 2 (n = 1) vertebral fracture. The 12-month vertebral fracture data were available for 23 participants (85.2%) in the alendronate group and 24 participants (82.8%) in the control group. Of these participants, no new grade 1 or grade 2 fractures were experienced in the alendronate group, and two participants in the control group experienced a new grade 1 fracture (difference not significant). All fractures occurred in the thoracic spine.

Quality of Life

The SF-36v2 physical component score (PCS) and mental component score (MCS) were similar at baseline between groups (Table 1). At follow-up, the mean changes in PCS and MCS were — 1.18 ± 4.93 and — 2.67 ± 7.55, respectively, in the alendronate group vs — 3.69 ± 8.33 and 3.26 ± 12.27, respectively, in the control group. While these changes were not significant between groups, the mean baseline and follow-up PCSs for the entire group and for each treatment group fell below the mean age-standardized and sex-standardized scores for Canadians. This statistical data is collected with My Canadian Pharmacy.

Safety Analysis

Table 2 presents the proportion of participants in the alendronate group and the control group who experienced adverse events, including serious events and drug-related events. Overall, seven participants (25.9%) in the alendronate group and three participants (10.3%) in the control group experienced a serious adverse event (difference not significant). Serious adverse events in the alendronate group were classified as exacerbation of CF (n = 3), bronchial superinfection (n = 1), hypoglycemic seizure (n = 1), GI (n = 1), and intestinal obstruction (n = 1). Three participants who experienced serious adverse events in the control group were classified as having an exacerbation of CF, with two of these participants reporting additional GI complaints. Table 3 provides a description of all GI-related adverse events that occurred over the course of the study. Ten GI-related events occurred in the alendronate group, and seven GI events occurred in the control group. The most common GI-related adverse events were nausea and/or vomiting.

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Table 1—Baseline Characteristics

Characteristics Alendronate Group (n = 27) Control Group (n = 29) Missing Cases (Alendronate Group/Control Group)
Gendert
Male 17 (63) 17 (59)
Female 10 (37) 12 (41)
Age, yr 28.1 (7.7) 30.9 (9.7) 0/0
Height, cm 169.1 (10.3) 165.3 (9.0) 0/0
Weight, kg 57.8(10.5) 62.0 (12.3) 0/0
Body mass index, kg/m2 20.1 (2.0) 22.6 (3.2) 0/0
FEVj
L 2.18(0.9) 1.98 (0.8) 0/0
% predicted 58.1 (21.9) 56.7 (20.7) 0/0
FVC
L 3.50(1.1) 3.18(1.1) 0/0
% predicted 79.4 (18.6) 79.9 (22.0) 1/1
Lumbar spine BMD, g/cm2 0.94 (0.12) 0.95 (0.10) 0/0
Lumbar spine T score — 1.64 (0.71) — 1.68 (0.75) 0/0
Total hip BMD, g/cm2 0.88 (0.15) 0.91 (0.11) 0/0
Total hip T— score — 1.01 (0.93) — 0.86 (0.65) 0/0
Calcium, mmol/L 2.34 (0.11) 2.29 (0.11) 0/0
Creatinine, |xmol/L 70.01 (11.33) 69.91 (13.9) 0/0
Albumin, g/L 40.9 (3.7) 39.1 (3.6) 0/0
Alkaline phosphatase, U/L 113.0 (72.7) 107.4 (32.6) 0/0
25-hydroxyvitamin D3, nmol/L 60.9 (28.4) 59.7 (28.0) 3/3
parathyroid hormone, pg/mL 36.1 (17.0) 45.9(22.1) 1/2
SF-36v2t
PCS 48.6 (6.4) 46.2 (6.9) 3/1
MCS 52.3 (9.0) 47.0 (9.6) 3/1

Table 2—Number of Participants With One or More Adverse Event

Alendronate Group (n = 27) Control Group (n = 29)
Variables INo. % No. %
Any AE 15 56 19 66
Serious AE 7t 26 3j 10
Drug-related AE 8 30 8 28

Table 3—Total GI-Related AEs

AEs Alendronate Group (n = 27) Control Group (n = 29)
Nausea and/or vomiting 3 4
Reflux 1 0
Difficulty swallowing 1 0
Esophagitis 1 0
Constipation 1 1
GI upset 1 0
Intestinal obstruction 1 1
Stomach pain/burn 1 1

Figure 1. Patient enrollment and follow-up.

Figure 1. Patient enrollment and follow-up.