JORT Journal

3.       Background

Osteoporosis is defined as a skeletal disorder leading to a systemic decrease in bone mass and an increased susceptibility to fractures [1-3]. This results in considerable impact on patient Health-Related Quality of Life (HRQL) and imposes a significant economic burden on our healthcare system [4-6].

Various drugs are available for the treatment of osteoporosis with the goal of reducing the morbidity and mortality associated with fractures and improving a patient’s HRQL. First line treatment typically involves bisphosphonates followed by denosumab, a monoclonal antibody targeting the Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) [7-9]. Teriparatide, a 34-amino acid formulation of recombinant human parathyroid hormone (PTH), is currently the only available anabolic agent for the treatment of osteoporosis.

Although sustained secretion of PTH decreases bone mass, intermittent pulsations of PTH has been shown to increase bone mass as is seen with studies of teriparatide showing increases in the rate of osteoblast development and prevention of osteoblast apoptosis [10-14]. Multiple studies have established the effectiveness of teriparatide in significantly improving Bone Mineral Density (BMD) at most sites including the lumbar spine, femoral neck and total hip as well as reducing the risk of vertebral and non-vertebral fractures [10,15,16]. Also well-established is the significant impact teriparatide has on HRQL during treatment, with some evidence emerging now suggesting that these benefits persist up to 18 months post discontinuation of teriparatide [17-20] 

Our retrospective chart review seeks to affirm the existing literature regarding the effects of teriparatide on BMD and HRQL over the duration of the therapy and, additionally, provide evidence demonstrating the sustained effects of teriparatide up to two years following completion of treatment.

4.       Materials and Methods

4.1.  Study Participants

This retrospective chart review was conducted in a single Canadian academic rheumatology practice on 167 osteoporosis patients (143 females and 24 males) who received teriparatide therapy for an 18-month regimen, as recommended at the approval of teriparatide in 2004, or a 24-month regimen, as recommended by current guidelines. Patients undertook treatment regimens from August 2004 to October 2013. Three reviewers (H.B., R.C. and A.B.) extracted data from an Electronic Medical Records (EMR) system and for patients who did not have an EMR, data was extracted via paper records by H.B. Data was abstracted regarding patient demographics, medication history, and mini-OQLQ scores and BMD. The Hamilton Integrated Research Ethics Board approved this study.

4.2.  Measurement of Health-related Quality of Life

HRQL was measured through the mini-OQLQ, a shortened version of the 30-item Osteoporosis Quality of Life Questionnaire (OQLQ), comprising of 10 questions that address the 5 domains: symptoms, physical function, activities of daily living, emotional function and leisure. A change of approximately 0.5 within each domain is considered a clinically relevant difference in quality of life [21]. The mini-OQLQ was administered prior to commencement of teriparatide therapy and at each subsequent follow-up visit, during teriparatide therapy as well as post-teriparatide therapy.

4.3.  Statistical Analyses

A repeated measures mixed-model analysis was utilized to compare baseline and follow-up measurements for BMD at three sites (femoral neck, lumbar spine and total hip) as well as each of the ten questions in the mini-OQLQ questionnaire. All analyses were adjusted for sex, baseline age, height and weight.

5.       Results

5.1.  Participant Characteristics

Our study included 167 patients with osteoporosis, 143 of whom were female. The mean age at onset of PTH therapy was 65.13 (SD = 11.36). The mean baseline T scores at the lumbar spine, femoral neck and total hip were -2.79 (SD = 1.30), -2.27 (SD = 0.97) and -1.93 (SD = 0.95) respectively (Table 1). 

Data regarding prior bisphosphonate use was available for 163 patients, with 30 patients not having previously used a bisphosphonate, 36 patients having used a bisphosphonate for three years or less and 53 patients having used a bisphosphonate for more than three years. The remaining 44 patients had used bisphosphonates in the past but details regarding time of bisphosphonate use were unavailable (Table 2). Table 2 additionally provides a list of prior drugs used by these 163 patients including antiresorptive agents (alendronate, risedronate, zoledronic acid, estrogens, raloxifene, calcitonin and denosumab), calcium and vitamin D.

5.1.  Effects of Teriparatide on BMD

At the lumbar spine site, we observed a statistically significant improvement from baseline T-scores at all three follow up visits post teriparatide therapy, showing a 0.84 g/cm² improvement by the final visit (p = <0.001). Improvements were seen in the two follow-up visits during teriparatide therapy, with the first follow-up demonstrating a 0.58 g/cm² improvement and second follow-up demonstrating a 0.92 g/cm² improvement. Both follow-ups were statistically significant (p = <0.001) (Table 3). 

At the femoral neck site, we observed an improvement from baseline T-scores at all three follow up visits up to two years post-teriparatide therapy, showing a 0.30 g/cm² improvement by the final visit (p = 0.007). Improvements were seen in the two follow-up visits during teriparatide therapy, with the first follow-up demonstrating a 0.05 g/cm² improvement and second follow-up demonstrating a 0.16 g/cm² improvement. Only the second follow-up was statistically significant (p = 0.04) (Table 3).

At the total hip site, we observed a statistically significant improvement from baseline T-scores at all three follow up visits post teriparatide therapy, showing a 0.26 g/cm² improvement by the final visit (p = 0.003). No changes were seen in the two follow-up visits during teriparatide therapy, with the first follow-up demonstrating a -0.01 g/cm² decrease in BMD and second follow-up demonstrating a 0.00 g/cm² change. Both follow-ups were not statistically significant changes (p-values 0.91 and 0.97 respectively) (Table 3). In subgroup analyses comparing previously treated osteoporosis patients to treatment-naïve patients, we noted no statistically significant differences in bone mineral density among patients who were treated with bisphosphonates either prior to or after commencement of teriparatide therapy, or patients who were treated with denosumab after commencement of teriparatide therapy (Table 4). 

5.3.1.         Symptoms: Questions 1 and 2 (Appendix) address the HRQL domain of symptoms. We noted statistically significant improvements from baseline of -0.63 for question 1 and -0.92 for question 2 at the second follow-up post teriparatide therapy (p = 0.005 and <0.001, respectively). All other follow-up scores showed statistically significant improvements except for questions 1 at the fourth follow-up during teriparatide therapy, which showed an improvement of -0.5 (p = 0.2).

5.3.2.         Emotional functioning: Questions 3 and 4 (Appendix) address the HRQL domain of emotional functioning. We noted statistically significant improvements from baseline of -0.9 for question 3 and -0.42 for question 4 at the second follow-up post teriparatide therapy (p = 0.001 and 0.04 respectively). All other follow-up scores were not statistically significant, except for question 3 at the third follow-up during teriparatide therapy, which showed an improvement of -0.63 (p = 0.026).

5.3.3.         Physical functioning: Questions 5 and 6 (Appendix) address the HRQL domain of physical functioning. We noted statistically significant improvements from baseline of -0.84 for question 5 and -0.67 for question 6 at the second follow-up post teriparatide therapy (p = 0.002 and 0.011 respectively). All other follow-up scores were not statistically significant, except for question 5 at the second follow-up during teriparatide therapy, which showed an improvement of -0.42 (p = 0.041) and question 6 at the first follow-up after teriparatide therapy, which showed an improvement of -0.41 (p = 0.046).

5.3.4.         Activities of daily living: Questions 7 and 8 (Appendix) address the HRQL domain of activities of daily living. We noted non-statistically significant improvements from baseline of -0.66 for question 7 and -0.44 for question 8 at the second follow-up post teriparatide therapy (p = 0.052 and 0.094 respectively). All other follow-up scores were not statistically significant.

5.3.5.           Leisure: Questions 9 and 10 (Appendix) address the HRQL domain of leisure. We noted non-statistically significant improvements from baseline of -0.34 for question 9 and -0.5 for question 10 at the second follow-up post teriparatide therapy (p = 0.165 and 0.093 respectively). All other follow-up scores were not statistically significant, except for question 9 at the second follow-up during teriparatide therapy, which showed an improvement of -0.38 (p = 0.05), question 9 at the first follow-up after teriparatide therapy, which showed an improvement of -0.48 (p = 0.013) and question 10 also at the first follow-up after teriparatide therapy, which showed an improvement of -0.56 (p = 0.023).

6.       Discussion

The results of our study support the existing literature in that treatment with teriparatide improves BMD at the lumbar spine, femoral neck and total hip sites regardless of prior treatment with or without antiresorptive agents [15,22]. These improvements were noted to persist at all three sites at the third follow-up post teriparatide therapy. Use of antiresorptive agents prior and after teriparatide therapy showed no statistically significant difference to patients naïve to antiresorptive therapy. With regards to benefits relating to HRQL, it is well documented in the literature that teriparatide treatment demonstrates significant benefits during the course of an 18 and 24-month treatment regimen, with evidence suggesting that these improvements in HRQL are superior to improvements gained through bisphosphonate treatment alone [18,23,24]. Following teriparatide treatment, literature regarding sustained improvements of HRQL is scarcer and mostly drawing from the European Forteo Observational Study (EFOS). In these studies, HRQL was measured using the EuroQol five dimensions questionnaire (EQ-5D) consisting of the 5 domains mobility, self-care, usual activities, pain/discomfort and anxiety/depression. All domains demonstrated sustained improvements at 18-months post teriparatide treatment [19,20]. In assessing HRQL during and post teriparatide treatment, our study utilized the mini-OQLQ, a shortened version of the OQLQ, which has been shown to be effective clinical tool in evaluating the health-related quality of life in osteoporotic women with back pain due to vertebral fractures [21]. The results of our study indicate significant improvements most notably in the symptoms, emotional functioning and physical functioning domains at the final follow-up post teriparatide therapy. The activities of daily living and leisure domains showed improvements at the final follow-up post teriparatide therapy, although they were not statistically significant. The reduction in the symptoms, emotional functioning and physical functioning domains indicate that patients who have received teriparatide therapy showed a reduction of distress or discomfort, are less fearful of fractures and falling and are able to perform more rigorous activity. Although possibly, partly attributable to alternate pharmacological treatments after completion of teriparatide, these improvements were sustained for up to 2 years following treatment.

Several important limitations of our study must be addressed. This was a retrospective cohort study, and comes with the known limitations of such a study design. Patients were not randomized to teriparatide versus standard therapy, and therefore our findings are susceptible to selection bias regarding patients who were eligible for teriparatide. Patients and physicians were not blinded to therapy, which may influence outcomes; though this is less significant with more objective scores such as BMD, it may play a role in the interpretation of more subjective outcomes such as self-reported HRQL symptoms. Our retrospective review did not have a control group, which would have been beneficial as a comparator for our study. Furthermore, the assumption was made that all patients were compliant with their teriparatide therapy. However, this is likely an over-estimate, and thus the effects of teriparatide therapy may have been understated in our analysis. Despite these limitations, the robust improvement in BMD, particularly at the lumbar spine, as well as in HRQL symptoms, is supportive of teriparatide as an effective anabolic agent for the treatment of osteoporosis.

7.       Conclusion

Our study is consistent with the literature in the effects of teriparatide treatment in increasing the BMD of patients treated for osteoporosis. BMD improvements were shown to extend for at least up to three follow-up visits or two years post teriparatide therapy. These BMD improvements are accompanied by significant improvements in various domains of the mini-OQLQ demonstrating an improvement in HRQL both during teriparatide treatment and subsequently up to two years post treatment.

8.       AppendixShortened Osteoporosis Quality of Life Questionnaire


1) How much distress or discomfort have you had because of pain in the last two weeks?
2) How much distress or discomfort you had in last two weeks because it had been painful to stand for a long time
3) How often in the last two weeks have you felt afraid of fractures?
4) How often in the last two weeks have you felt afraid of falling?
5) How difficult has it been for you to lift things in the last two weeks?
6) How difficult has it been for you to carry things in the last two weeks, because of back problems due to osteoporosis?
7) How difficult has it been for you to vacuum in the last two weeks?
8) How difficult has it been for you to housework in the last two weeks?
9) How difficult has it been for you to travel in the last two weeks?
10) How difficult has it been for you to take the type of vacation or holiday you enjoy because of your back
problems due to osteoporosis 

Table 1: Baseline characteristics of patients receiving teriparatide therapy.

Medical histories regarding hysterectomies, oophorectomies and time since last periods were available for 142 of the female patients (Table 2).

Table 2: Medical histories and medications use.

Table 3: BMD changes compared to baseline at all follow-ups during and after teriparatide therapy.

Table 4: Antiresorptive agent effect on BMD compared to naïve patients averaged over all time points

Table 5: Quality of life scores compared to baseline at all follow-ups during and after teriparatide therapy

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