Changes in dispensing of anti-osteoporotic drugs during COVID-19 pandemic

Care of osteoporosis patients during COVID-19 pandemic is challenging. Due to lockdowns and restrictions, the management of osteoporosis has changed. Diagnosis of osteoporosis decreased and the influence of COVID-19 on drug prescriptions and dispensing is currently unclear. Therefore, the aim of the study was to assess the dispensing of anti-osteoporotic drugs during the Covid19 pandemic. Methods This study was a nationwide retrospective register-based observational study which included all patients in Austria aged >= 50 who received at least one prescription for anti-osteoporotic drug between January 2016 and November 2020. Pseudonymized individual-level patients' data were obtained from social insurance authorities and the Federal Ministry of Labour, Social Affairs, Health and Consumer Protection in Austria. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) Denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) for the prediction of drug dispensing. Results There were 2,884,627 dispensing of anti-osteoporotic drugs by 318,573 patients between 2016-2020. The mean monthly prescriptions for oral bisphosphonates (-14.5 %) and SERMs (-12.9 %) decreased during COVID-19 pandemic, compared to the non-COVID-19 period. The dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased during COVID- 19. The prescriptions for DMAB decreased during the first lock-down in March and April 2020 (24 %), however increased by 29.1 % for the total observation time. The ARIMA model for alendronate showed, that the estimated step change was minus 1443 dispensing (95 % CI - 2870 to - 17), while the estimated change in slope was minus 29 dispensing per month (95 % CI - 327 to 270). Thus, there were 1472 (1443 + 29) fewer dispensing in March 2020 than predicted had the lockdown not occurred. Discussion The total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during the first COVID-19 lockdown. The largest drops in absolute terms were observed for ibandronate, followed by alendronate, denosumab, zolendronic acid and risendronate. The observed decrease of DMAB during the first lockdown, was compensated in the following months. Current evidence suggests no need for discontinuation of anti-osteoporotic drugs during COVID-19 pandemic, nor because of vaccination. Taking into account the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even in times of pandemics.

IMPACT of the SARS-COV 2 PANDEMIC and RELATED EPIDEMIOLOGICAL RESTRICTIONS on the CARE of PATIENTS with OSTEOPOROSIS-EXPERIENCES of A HUNGARIAN CENTRE

Background: Treatment of patients with osteoporosis was inadequate even before the COVID-19 pandemic. Not only patients without fracture, but only a small proportion of patients with osteoporotic fracture have treated. In Hungary only 30% of patients with osteoporosis received adequate antiporotic treatment before the pandemic. Almost 90% of whom were women, less than 10% of men. The incidence of fractures is increasing dramatically worldwide. In 2010, the vertebral fracture rate was 3.5 million in Europe but it is expected to reach 4.5 million by 2025. In 1990, osteoporosis caused 1.26 million hip fractures and by 2025 this is estimated at 2.6 million worldwide. The care for patients with osteoporosis was further aggravated by the restrictions necessarily imposed due to the coronavirus. Objectives: The aim of the study was to explore the extent and consequences of diagnostic and therapeutic failure in patients with osteoporosis. Methods: I determined the number of osteoporosis examinations performed in our centre in 2019-2021 from the medical database. I surveyed how many patients were discontinued the antiporotic treatment during the pandemic according to the different drug groups in Hungary and also in our centre as well as the prevalence of wrist and hip fractures due to minor trauma in our county in the pre-and post-pandemic period. Results: In our centre an average of 30 DEXA examinations were performed daily in the pre-pandemic period. From the end of October 2021 to the end of May 2021 there was not perform any ODM examinations. It means 3.980 missed exams and at least 1.000 missed osteoporosis diagnoses and therapy starts. More than 20% of patient were lost from the antiporotic care in Hungary. Drop-out was mainly seen in patients treated with bisphosphonates. There were 20730 bisphosphonate-treated patient in 2019, 19813 in 2020 and 17315 in 2021. Antiporotic treatment was discontinued in 30% of patients treated with bisphosphonate+vitamin-D (7849 in 2019, 6950 in 2020, 5484 in 2021) or bisphosphonate+calcium+vitamin-D fxed combination products (3256-2876-2289). In our centre, the prescribing of bisphosphonates has also decreased more than half. Patients treated with iv. bisphosphonates were interrupted or switched to oral formulations. Denosumab therapy was continuous: 581 injections were prescribed in the 12 months before and 579 during the pandemic. However, no new treatment started. In case of teriparatide, the initiated therapies were continued and even the number of prescriptions increased. As a consequence, an increase in the occurrence of fractures due to minor trauma is expected. Although epidemiological restrictions in this regard, the curfew has had some positive effects. According to international data, the number of wrist fractures has almost halved, while the data for hip fractures are controversial. The decrease of wrist fractures can also be verifed in our county. The number of wrist fractures was 598 in April-May 2019, 393 in the same period in 2020, and 372 in 2021. After a signifcant reduction in hip fractures in 2020, there is already an upward trend in 2021 (470 in 2019, 358 in 2020, 393 in 2021). The real consequences of failure to treat osteoporosis are expected only after years. Conclusion: Missed doctor-patient appointments were associated with missed diagnoses and interruptions of ongoing treatments. Fear of the virus, immobilisation due to home office and curfews, lack of exercise, sun exposure, caused depressive symptoms, increased alcohol consumption and caloric intake are all increase the risk of osteoporosis. Thus, traditional risk factors for osteoporosis expanded with the direct effects and the introduced restrictions because of the pandemic.

PHARMACIST-LED OSTEOPOROSIS TELEPHONE SERVICE

Background/Aims The COVID-19 pandemic has made finding ways to consult suitable patients remotely a priority. We have introduced a telephone assessment clinic, run by our departmental pharmacist, to assess and treat patients with osteoporosis who have been referred from primary care for consideration of parenteral bone sparing therapy. Methods Patients with osteoporosis who have been referred from primary care were triaged electronically into a fortnightly telephone assessment clinic, according to pre-specified criteria. Prior to the appointment, information leaflets about osteoporosis, and treatments for this condition were posted to the patients. The telephone consultation was carried out and patient demographics, risk factors for fracture, bone density results, FRAX / NOGG assessment, treatment decisions, and other clinical details were recorded on a pro-forma. A satisfaction survey was sent out to each patient following consultation. Results Sixty patients were assessed between July 2020 and April 2021. Fiftyseven (95%) were female, and the mean age was 71 years. Following consultation, twenty-one were commenced on zoledronic acid, eighteen on denosumab, three on teriparatide and eighteen no treatments /other. Average time from referral to consultation was 1.75 months. Thirty-four patient satisfaction surveys were returned. Twenty-nine (85%) patients said they would be happy for consultations via telephone in the future, with twenty-five patients (74%) either likely or highly likely to recommend telephone consultation to family or friends. When asked to compare their experience of telephone to faceto- face consultations;twenty (58%) reported being indifferent, four (12%) said their experience was poorer or significantly poorer than face-to-face, and ten (29%) said their experience was better or significantly better. Mean saving on travel expenses was £0-£5 (41% of patients) with four patients (12%) saving £21+. Mean mileage saved was < 5 miles (33% of patients), with seven patients (21%) saving 30+ miles on travel. Conclusion This study reveals that patients, overall, had a positive experience with a pharmacist-led telephone consultation. Such clinics could be implemented across other areas of our rheumatology service, if clinically appropriate;reducing unnecessary patient contact, reducing consultant work load and optimally utilizing skills of the wider multidisciplinary team. Face-to-face consultations still have an essential role where physical examination may be required, or patients have communication barriers. Our sample size was small, and data collection is on-going.

Osteoporosis care during the COVID-19 pandemic

COVID-19 is an emerging infectious disease that has specific characteristics that interfere with the care of patients with osteoporosis. This article discusses the interfaces between osteological issues and COVID-19. A prevalent fracture very modestly increases the risk of death from COVID-19 but in hospitalized patients, the prevalence of vertebral fracture can be considered another aspect of polymorbidity increasing the likelihood of an adverse course of infection. Vitamin D deficiency correlates with worse outcomes in COVID-19, and sufficient vitamin D saturation is very likely protective in relation to COVID-19. Containment measures at the peak of the pandemic may result in muscle loss and increased risk of falls in the elderly. Densitometry and majority of laboratory tests can be easily delayed in patients with osteoporosis. This also applies to parenteral administration of bisphosphonates, whereas continuation of oral bisphosphonate therapy can be ensured by electronic prescription. Teriparatide should not be discontinued for more than 2–3 months, and the interval between denosumab administrations should not exceed 7 months.

Telemedicine in Patients with Fragility Fractures in the COVID-19 Era

Introduction: The covid19 pandemic has forced the health system to restructure to prevent contagion of our patients. In this context, the members of the Orthogeriatric Group of the Catalan Society of Geriatrics and Gerontology (SCGiG) created a document that collected all the considerations to take into account during the pandemic, based on the current guides and scientific societies, in order to perform a correct follow-up, enhance adherence and prevent future falls. Methods: A bibliographic review was performed, defining the key points in the care of the fractured patient through telemedicine (document is available at http://scgig.cat/docs/gt-orto-covid.pdf). Results: During hospital admission, antiosteoporotic treatment should be started, evaluating indications with the patient and family, to ensure adherence. Diet intake of calcium and vitamin D will be assessed. Discharge report includes evaluation of treatment and monitoring plan, to be useful for liaison nurse, rehabilitator and general practitioner. Six-monthly follow up is recommended for patients with comorbidities, polypharmacy, confusion, fall-risk, or parenteral anti-osteoporotic treatment. With denosumab or teriparatide, annual laboratory tests are recommended, with GFR <20, every six months, at home if possible. Bisphosphonates can be followed by the GP. Zoledronate is not recommended due to delayed administration after surgery, and possibility of transient flu-like simptoms. In the telematic follow-up visit, in patients undergoing zoledronic acid treatment, the new dose can be delayed for 6-12 months, without risk. Consider sequential treatment. Denosumab treatment cannot be delayed, so the patient and family will be trained in self-administration. Support materials from laboratories will be useful to patient and caregivers. Conclusion: Telemedicine is a good strategy for a follow-up, to avoid hospital contact, and starts on hospital admission. Patient and caregivers need access to new technologies and able to understand medical instructions.

Self-injection of denosumab in clinical practice in the french pilote study

Objective: Describe characteristics of patients who self-inject denosumab and patterns of self-injection in France. Methods: PILOTE was a prospective observational study that evaluated persistence to denosumab over 24 months in France in postmenopausal women. Clinical information obtained through routine practice was recorded onto an eCRF, including the individual who injected subcutaneous denosumab (physician, nurse, patient, other). We conducted an ad hoc analysis of the patients in the study who self-injected denosumab. Results: In total, 478 patients were enrolled between June 2105 and February 2016. 27 patients self-injected denosumab at least once, with these patients distributed across multiple sites. Those who self-injected appeared slightly younger with longer duration of osteoporosis, and a higher proportion had a prior fracture and previous glucocorticoid and teriparatide treatment than the overall population (Table). Self-injected patients were also more likely to be living at home with family, have a University education, and be seen by a rheumatologist than a GP. Twelve patients self-injected from the beginning of the study, 15 self-injected after receiving injection from an HCP and 8 switched back to HCP injections after self-injection. Eleven of the 12 patients who self-injected from the beginning were persistent at 24 months. Six ADRs occurred in three self-injecting patients: one vertebral fracture, bone pain, muscle fatigue, myalgia, asthenia, pyelonephritis. Conclusion: Although numbers were small, self- administration of denosumab appeared feasible for women with postmenopausal osteoporosis and may be a valuable option, particularly in the context of the COVID-19 pandemic when office visits are restricted. (Table Presented).

Severe osteoporosis: Pandemic pick ups

Objective: During COVID-19 pandemic, the access to skeleton investigations for osteoporosis was in many cases postponed, thus consequences on fracture risk (FR) might be expected in terms of not continuing the antiosteoporotic medication or not initiating it if needed. Reduced physical activity might reduce the risk of fall, on one hand, but associated sarcopenia and inhibition of bone formation due to lack of physical exercise increase the FR, on the other hand (1-5). This is a case report of a female with severe osteoporosis who delayed the presentation for diagnostic during first 15 months of pandemic. Case report: This is a 73-year-old female, known with a history of osteoporosis since 2005. She also associates FR: chronic therapy with different SSRIs for depression, multinodular goiter-related hyperthyroidism (which was treated with radioiodine therapy). She has chronic therapy for arteria hypertension, hyperlipemia and hiatal hernia. At diagnostic, after initial lumbar T-score=-3.5 SD, she refused therapy until 2015 (when T-score decreased to -4 SD), thus she began therapy with intravenous ibandronate until 2017 when she experienced a vertebral fracture and daily 20 μg of teriparatide was initiated, starting from a DXA-BMD of 0.783 g/cm2, T-score of 3.1 SD. After 8 months, the treatment was stopped because of her lack of compliance, so she continued with annual zolendronic acid 5 mg until of T-score of -2.6 SD, BMD=0.856 g/cm2. In March 2020, when lockdown pandemic were initiated, she had to come to reassessment, but delayed it, and refused medication based on telemedicine recommendations, except for daily 1000 UI vitamin D. 14 months later, central DXA showed lumbar L1-3 BMD of 0.824 g/cm2, T-score of -2.9 SD, Z-score of -0.7 SD, hip BMD of 0.682 g/cm2, T-score of -2.6 SD, Z-score of -0.4 SD;25-hydroxyvitamin D of 29 ng/mL, PTH of 55 pg/mL, suppressed CrossLaps of 0.287 ng/mL (normal: 0.33-0.782 ng/mL), osteocalcin of 17 ng/mL (normal: 15-46 ng/ mL), P1NP of 27 pg/mL (normal: 15-45 pg/mL);an additional T4 thoracic fracture. Zolendronic acid was further recommended. Conclusion: During pandemic lockdown, the usual serial assays and decision of therapy were less adequate based on telemedicine.

Zolendronic acid after teriparatide: Pandemic observations

Objective: Teriparatide for sever osteoporosis is followed by antiresorptive drugs, and one option in patients with gastric intolerance is zolendronic acid or denosumab (1-5). During pandemic lockdown, the access to bone assessment was limited (1-5). Type 1 diabetic patients are particularly at risk for bone loss, but also for COVID-19 infection, thus the importance of respecting the pandemic rules (1-5). We aim to introduce a female case diagnosed with severe menopausal osteoporosis that was followed during post-teriparatide sequence of medication, including during pandemic days. Case report: This is a type 1 diabetic female of 77 y who was first diagnosed with menopausal osteoporosis 8 y ago (lumbar T-score of-3.1 SD) and started medication with weekly alendronate in addition to vitamin D supplements. After 3 y, she suffered a single spontaneous vertebral fracture thus teriparatide was initiated for 2 y (with good tolerance): lumbar T-score went from -3.1 to -1.9 SD. In the meantime, due to bilateral coxarthrosis she needed bilateral hip replacement. Further on, she continued with biannually denosumab for 8 injections, reaching a lumbar BMD-DXA 0.942 g/cm2, T-score of -2 SD, Z-score of -0.8 SD so an intravenous perfusion with zolendronic acid 5 mg was administered plus vitamin D supplements. While she had no additional fracture and glycated haemoglobin A1c remained around 6.2-6.4%, one year later, the pandemic started, so only bone turnover markers (BTM) were assessed, not DXA: suppressed CrossLaps=0.22 ng/mL (normal: 0.33-0.782 ng/ mL), osteocalcin=11 ng/mL (normal: 15-46 ng/mL), P1NP=27 pg/mL (normal: 15-45 pg/mL). She continued with vitamin D, and 20 months after injection CrossLaps remained low (=22 ng/mL) with normal osteocalcin (=15 ng/mL), P1NP (=28 pg/mL) and stationary BMD. Conclusion: Zolendronic acid effect in osteoporotic patients is easy to access by blood assays if DXA is not available, while lack of BTM increase is suggestive for a good outcome.