Discontinuation Of Teriparatide Research Articles

Comparison of the Continuation Rate of Twice-Weekly and Weekly Teriparatide Administration in a Rural Area.

Teriparatide plays an important role in the treatment of patients with severe osteoporosis; however, it is meaningless if patients cannot continue. In recent years, the use of a twice-weekly auto-injector teriparatide preparation has become possible. However, its continuation rate and the factors affecting it have not been adequately investigated. Therefore, this study aimed to examine the continuation rate of twice-weekly teriparatide and the factors affecting it. This retrospective study included 143 patients who were administered teriparatide weekly (65 patients) or twice-weekly (78 patients) in a rural hospital. Patient information, such as age, the distance between the hospital and home, family structure, past osteoporosis treatment and fracture, adverse events, and period of teriparatide continuation, were collected. We compared the differences in continuation rates between the twice-weekly and the weekly groups using the Kaplan-Meier curves, and we examined factors influencing teriparatide discontinuation using multivariate analyses. The 12- and 24-month continuation rates of twice-weekly administration of teriparatide were 79.5% and 61%, respectively. The twice-weekly group showed a significantly higher continuation rate (P < 0.0001). The multivariate analyses showed that older age and adverse events were identified as risk factors negatively influencing teriparatide continuation (P = 0.0237 and P < 0.0001, respectively). On the other hand, twice-weekly teriparatide was shown to reduce the risk of discontinuation (P = 0.0043). The twice-weekly teriparatide has a considerably higher continuation rate than the weekly teriparatide. Weekly preparation, older age, and adverse event were identified as risk factors negatively influencing teriparatide continuation.

Bone Density After Teriparatide Discontinuation With or Without Antiresorptive Therapy in Pregnancy- and Lactation-Associated Osteoporosis.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare and severe disorder that causes low-trauma or spontaneous fractures, most commonly multiple vertebral fractures, in the late pregnancy or lactation period[1]. In severe PLO, teriparatide (TPTD) might aid in bone mineral density (BMD) recovery and subsequent fracture risk reduction. However, it is unclear whether TPTD can be discontinued without sequential antiresorptive therapy (ART) in premenopausal women with PLO. In this retrospective cohort study, we investigated the changes in BMD in premenopausal women with PLO treated with TPTD 20 mcg daily with or without sequential ART. Data for 67 patients diagnosed with PLO from 2007 through 2017 were reviewed. Among 43 women with annual follow-up dual-energy X-ray absorptiometry data for 3years, 33 were treated with TPTD (median 12months) with (TPTD-ART, n = 13; median, 18months) or without (TPTD-no ART, n = 20) sequential ART. The two groups showed no differences in the mean age (31 vs. 31years), body mass index (BMI, 20.5 vs. 21.0kg/m2), and baseline lumbar spine (LS) BMD (0.666 vs. 0.707g/cm2; p > 0.05 for all). LSBMD increased at 1, 2, and 3years from baseline in both the TPTD-ART (14.1%, 21.8%, and 24.0%, respectively) and TPTD-no ART (17.3%, 24.1%, and 23.4%, respectively) groups, without significant between-group differences. Similar results were observed for the total hip BMD. LSBMD gain at 3years did not differ by ART use (adjusted β, 0.40; p = 0.874) in univariable and multivariable models adjusted for age, BMI, and baseline LSBMD. In summary, BMD gain by TPTD administration in premenopausal women with PLO can be well maintained without sequential ART treatment.

Patterns of Teriparatide and Sequential Antiresorptive Agent Treatment Among Elderly Female Medicare Beneficiaries.

The 2020 American Association of Clinical Endocrinologists guidelines for assessing osteoporosis among postmenopausal women stratified postmenopausal women with osteoporosis to "high" and "very-high" fracture risk categories and recommended anabolic agents as initial therapy followed by an antiresorptive agent. Switching the order can blunt the effect of anabolic agents, and failing to follow with an antiresorptive can lead to loss of bone generated by the anabolic agent. It would be helpful to understand the real-world prescribing patterns of anabolic agents. Using the 2010-2015 Medicare 100% osteoporosis database, we assessed patient profiles, teriparatide prescribers, persistence of teriparatide therapy, and antiresorptive agent use after teriparatide discontinuation among elderly women who initiated teriparatide from 2011 to 2013. This study included 14,786 patients. In the year before teriparatide initiation, 30.0% of them had a fracture, 67.6% had a dual energy x-ray absorptiometry scan, 74.4% had a diagnosis of osteoporosis, and 47.9% used antiresorptive agents (non-naïve teriparatide users). Among those who had fractures, 49.4% initiated teriparatide within 3 months postfracture. Teriparatide was prescribed for 37% of users by primary care doctors, 19% by rheumatologists, 13% by endocrinologists, and 7.0% by orthopedists. Median time of teriparatide use was 7.2 months. After teriparatide discontinuation, 40.8% switched to antiresorptive agents (31.9% among naïve teriparatide users, 50.5% among non-naïve users). Among switchers, 42.5% switched within 60 days, 50.5% switched to denosumab, and 31.6% switched to oral bisphosphonates. This study of real-world prescribing data found that about half of teriparatide users switched from an antiresorptive agent, and less than half switched to antiresorptive agents after teriparatide discontinuation. Persistence of teriparatide use was suboptimal. In the management of postmenopausal osteoporosis, increasing the persistence of teriparatide use and improving the appropriate treatment sequence of anabolic and antiresorptive drugs are critical to maximizing gains in bone mass, providing the greatest protection against fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

SAT-505 A Rare Case of Teriparatide Induced Persistent Hypercalcemia

INTRODUCTION Teriparatide is a recombinant endogenous parathyroid hormone. It is an anabolic medication which is FDA approved for treating Osteoporosis in postmenopausal women, men with primary or hypogonadal osteoporosis and Glucocorticoid-induced osteoporosis. Transient hypercalcemia with Teriparatide is reported in 1-3% of patients, 4-6 hours after the dose administration and lasts for 24 hours. It is thought to be through the increased renal production of 1,25-dihydroxy vitamin D, increased intestinal calcium absorption and inhibition of renal calcium excretion. We report a case of persistent hypercalcemia with Teriparatide use. CASE REPORT: A 74-year-old Caucasian female presented to the hospital with mental status changes, generalized bone pain, weight loss, and poor oral intake. Her past medical history includes Rheumatoid arthritis, Sjogren syndrome, osteoporosis with compression fractures and osteoarthritis of multiple joints. Patient’s medications include Prednisone 5 mg daily, calcitonin nasal spray, vitamin D and calcium supplements. She had previously failed bisphosphonate therapy for osteoporosis. She developed new compression fracture of L4 vertebra while being treated with Denosumab. Hence Teriparatide was started 4 months prior and she received the last dose 3 days prior to the presentation On presentation, she was noted to have severe hypercalcemia with total calcium of 17.3 mg/dL, ionized calcium of 9.4 mg/dL, albumin of 3.2 g/dL and a suppressed PTH of 3ng/L. Laboratory workup including renal function, phosphorus level, 25-hydroxyvitamin D level, 1,25-dihydroxy vitamin D, Parathyroid hormone-related peptide, Thyroid stimulating hormone, serum, and urine protein electrophoresis was unremarkable. CT scan of the neck, chest, abdomen, and pelvis showed no mass lesions or lymphadenopathy. An extensive evaluation failed to identify other causes of hypercalcemia except for immobilization. She was treated as a new onset Non-PTH dependent severe Hypercalcemia case. The patient had multiple admissions with recurrent hypercalcemia since then despite discontinuation of Teriparatide. Her calcium level normalized transiently with Intravenous fluids, an Intravenous bisphosphonate, and calcitonin. However, such treatment failed to maintain normal calcium level for more than 3-4 weeks.DISCUSSION Recurrent severe hypercalcemia with Teriparatide use is rarely reported. Although immobilization can precipitate hypercalcemia, immobilization is rarely a sole etiology of severe hypercalcemia. Our case report suggests that severe recurrent hypercalcemia can be associated with teriparatide use especially in the setting of immobilization. As far as we are aware, this is the fourth reported case of persistent hypercalcemia with Teriparatide use. This case highlights the importance of monitoring calcium levels periodically when Teriparatide is used.

Fracture Risk Following Discontinuation of Teriparatide: A Review of the Literature.

To review and summarize studies on the changes in bone mineral density (BMD) and fracture risk following discontinuation of teriparatide therapy. A search of PubMed (1966-May 2016) and International Pharmaceutical Abstracts (1970-May 2016) was conducted using the Medical Subject Headings terms teriparatide, osteoporosis, and withholding treatment. Free text searches included drug holiday, discontinuation, and drug discontinuation. These searches yielded 79 articles. There were 7 articles reviewed that addressed the effects of teriparatide discontinuation on markers of overall bone health and fracture risk. Teriparatide is a recombinant human parathyroid hormone that is indicated for a lifetime maximum of 24 months in the United States for the treatment of osteoporosis in men and women at high fracture risk. There is inconsistent evidence regarding retained skeletal integrity resulting from increased bone resorption. Study analyses have shown that female patients seem to have more reduction in BMD upon teriparatide discontinuation. Several studies evaluating teriparatide discontinuation were follow-up studies with small patient populations, limiting the generalizability and statistical rigor associated with assessing these outcomes. In addition, the majority of patients were receiving bisphosphonate therapy, and the true effect of discontinuing teriparatide remains unknown. Independent patient risk factors should be taken into consideration when weighing the risk-vs.-benefit of initiating and discontinuing teriparatide therapy. Additional randomized control trials should be conducted to determine long-term effects of discontinuing teriparatide in the presence and absence of other bone-strengthening agents.

The effect of switching from teriparatide to anti-RANKL antibody on cancellous and cortical bone in ovariectomized mice

We examined the effect of teriparatide, and switching from teriparatide to anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody, in ovariectomized mice. Twelve-week-old female C57BL/6 mice were ovariectomized or sham operated. Four weeks after surgery, ovariectomized mice were subjected to one of the following four treatments: phosphate-buffered saline (PBS) for 8weeks; teriparatide for 4weeks followed by PBS for 4weeks (PTH4W group); teriparatide for 8weeks (PTH8W group); or teriparatide for 4weeks followed by anti-RANKL antibody (single subcutaneous injection of 5mg/kg) (SWITCH group). Twelve weeks after the operation, bone mineral density was increased in PTH8W and SWITCH groups to broadly comparable levels, but these were significantly decreased in the PTH4W group after discontinuation of teriparatide. Histomorphometric analysis demonstrated that cancellous bone formation and resorption were profoundly suppressed in the SWITCH group. Bone formation was also suppressed on the endocortical surface of cortical bone but was maintained on the periosteal surface. Anti-RANKL antibody suppressed osteoclast activity immediately after treatment, while bone formation was only gradually decreased. These results suggest that anti-RANKL antibody may be a therapeutic option after discontinuation of teriparatide therapy.

Teriparatide discontinuation in a patient with post surgical hypoparathyroidism: a clinical challenge

Teriparatide discontinuation in a patient with post surgical hypoparathyroidism: a clinical challenge

Suitability of teriparatide and level of acceptance of pharmacotherapeutic recommendations in a healthcare management area

ObjectiveTo analyse the suitability of teriparatide prescriptions for osteoporosis treatment in a health management area, as well as the level of acceptance of pharmacotherapeutic recommendations made to physicians. DesignA prospective interventional study conducted from february 2015 to june 2015. SettingSouth Seville Health Management Area. ParticipantsPatients receiving teriparatide. Main measurementsSuitability of teriparatide prescriptions according to Clinical Practice Guidelines and level of acceptance of pharmacotherapeutic recommendations. ResultsTeriparatide prescriptions were unsuitable in 45 patients (68.2%); 11 due to no indication, 17 patients did not have previous treatments with first-line drugs, 6 due to contraindications and 9 patients were treated for more than 24 months with the drug. Besides, 4 prescriptions were unsuitable because of combination with other therapies. The acceptance of pharmacotherapeutic recommendations was 64.4%, leading to teriparatide discontinuation in 21 patients (72.4%), and a switch to alendronate or ibandronate in another 8 patients. ConclusionsA high percentage of teriparatide prescriptions is unsuitable in our health care management area, but it has decreased after pharmacist intervention.

Effectiveness of Teriparatide in Women Over 75 Years of Age with Severe Osteoporosis: 36-Month Results from the European Forsteo Observational Study (EFOS)

This predefined analysis of the European Forsteo Observational Study (EFOS) aimed to describe clinical fracture incidence, back pain, and health-related quality of life (HRQoL) during 18 months of teriparatide treatment and 18 months post-teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged ≥75 years. Data on clinical fractures, back pain (visual analogue scale, VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. A repeated-measures model analyzed changes from baseline in back pain VAS and EQ-VAS. During the 36-month observation period, 87 (14.8 %) women aged ≥75 years sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74 (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 % in the 30 to <36–month interval compared with the first 6-month interval (P < 0.009). Although the older subgroup had higher back pain scores and poorer HRQoL at baseline than the younger subgroup, both age groups showed significant reductions in back pain and improvements in HRQoL postbaseline. In conclusion, women aged ≥75 years with severe postmenopausal osteoporosis treated with teriparatide in normal clinical practice showed a reduced clinical fracture incidence by 30 months compared with baseline. An improvement in HRQoL and, possibly, an early and significant reduction in back pain were also observed, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication. The results should be interpreted in the context of an uncontrolled observational study.

A Case of Severe Hypercalcemia after Treatment with Teriparatide for Osteoporosis

Recombinant human parathyroid hormone 1-34 (rHPTH; 1-34, teriparatide) increases bone mass and increases osteoporotic fracture by stimulating new bone formation. It was approved in the United States for treatment of osteoporosis in men and women, and its effectiveness and safety was proved. Mild hypercalcemia was observed, but persistent and severe hypercalcemia was not observed in the studies of teriparatide. In this case, severe hypercalcemia was developed from patient having gait disturbance who was treated with vitamin D, calcium and teripartide for two months to treat osteoporosis after subtrochanteric fracture. Hypercalcemia was resolved with discontinuation of teriparatide. Severe hypercalcemia is not a common complication of teriparatide and monitoring of serum calcium level is routinely not recommended. But it is necessary to pay close attention to patients who were treated with teriparatide, especially in immobilized patients. [Korean Journal of Bone Metabolism, 19(1): 53-57, 2012]

Fracture rate and back pain during and after discontinuation of teriparatide: 36-month data from the European Forsteo Observational Study (EFOS)

SummaryIn this observational study in postmenopausal women with severe osteoporosis, the incidence of fractures was decreased during 18 months of teriparatide treatment with no evidence of further change in the subsequent 18-month post-teriparatide period when most patients took other osteoporosis medications. Fracture reduction was accompanied by reductions in back pain.IntroductionTo describe fracture outcomes and back pain in postmenopausal women with severe osteoporosis during 18 months of teriparatide treatment and 18 months post-teriparatide in normal clinical practice.MethodsThe European Forsteo Observational Study (EFOS) was a prospective, multinational, observational study. Data on incident clinical fractures and back pain (100 mm Visual Analogue Scale [VAS] and questionnaire) were collected. Fracture data were summarised in 6-month intervals and analysed using logistic regression with repeated measures. Changes from baseline in back pain VAS were analysed using a repeated measures model.ResultsA total of 208 (13.2%) of 1,576 patients sustained 258 fractures during 36 months of follow-up: 34% were clinical vertebral fractures and 66% non-vertebral fractures. The adjusted odds of fracture were reduced during teriparatide treatment and there was no evidence of further change in the 18-month post-teriparatide period, during which 63.3% patients took bisphosphonates. A 74% decrease in the adjusted odds of fracture in the 30- to <36-month period compared with the first 6-month period was observed (p < 0.001). Back pain decreased during teriparatide treatment and this decrease was sustained after teriparatide discontinuation. Adjusted mean back pain VAS decreased by 26.3 mm after 36 months (p < 0.001) from baseline mean of 57.8 mm.ConclusionsIn a real-life clinical setting, the risk of fracture decreased during teriparatide treatment, with no evidence of further change after teriparatide was discontinued. The changes in back pain seen during treatment were maintained for at least 18 months after teriparatide discontinuation. These results should be interpreted in the context of the design of an observational study.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-010-1498-5) contains supplementary material, which is available to authorized users.

Sequential Treatment of Severe Postmenopausal Osteoporosis After Teriparatide: Final Results of the Randomized, Controlled European Study of Forsteo (EUROFORS)

It is unclear which treatment should be given after stopping teriparatide therapy for severe osteoporosis. In a prospective, randomized, controlled, 2-yr study, we compared BMD effects and clinical safety of three follow-up treatments (anabolic with teriparatide, antiresorptive with raloxifene, or no active treatment) after 1 yr of teriparatide. Postmenopausal women with osteoporosis and a recent fragility fracture received open-label teriparatide (20 microg/d) for 12 mo before they were randomized (3:1:1) to continue teriparatide (n = 305), switch to raloxifene 60 mg/d (n = 100), or receive no active treatment for the second year (n = 102). All patients received calcium and vitamin D supplementation. Changes in areal BMD from baseline to 24 mo were analyzed using mixed-model repeated measures. Daily teriparatide treatment for 2 yr significantly increased spine BMD by 10.7%. Patients receiving raloxifene in year 2 had no further change in spine BMD from year 1 (change from baseline, 7.9%), whereas patients receiving no active treatment had a BMD decrease of 2.5% in year 2 (change from baseline, +3.8%). At the total hip, BMD increases from baseline at 2 yr were 2.5% with teriparatide, 2.3% with raloxifene, and 0.5% with no active treatment; the respective changes at the femoral neck were 3.5%, 3.1%, and 1.3%. The study had insufficient power to assess antifracture efficacy. In conclusion, BMD increases progressively over 2 yr of teriparatide therapy in women with severe osteoporosis. After discontinuation of teriparatide, raloxifene maintains spine BMD and increases hip BMD.

Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis

Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. Following a year of open-label teriparatide 20 mug/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (-1.0 +/- 0.3%, P = 0.004; and -4.0 +/- 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (-2.6 +/- 0.4% (raloxifene-raloxifene) and -2.7 +/- 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 +/- 0.5% vs. 5.1 +/- 0.5%; FN: 3.4 +/- 0.6% vs. 3.0 +/- 0.5%). Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment.

Sustained Nonvertebral Fragility Fracture Risk Reduction After Discontinuation of Teriparatide Treatment

A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 microg) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture. Treatment with teriparatide [rhPTH(1-34)] 20 and 40 microg once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months. All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction. Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p < 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p < 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 mug and combined groups versus placebo but not for the 20 microg group versus placebo. However, the 20 and 40 microg groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p = 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment. While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment.