The problem of low adherence to antiresorptive therapy with bisphosphonates: solutions

Over the past several decades, there has been a global aging of the population around the world. The demographic situation in the Russian Federation is no exception, being a natural result of an increase in the life expectancy of the population. In clinical practice, geriatric diseases have been identified and are widely studied, which deserve priority attention due to a sharp decline in the quality of life of elderly patients. Osteoporosis is called a “silent epidemic” among elderly and senile patients. This disease is associated with a high risk of low-traumatic fractures of various localization. The imperfect rehabilitation program after complex fractures and its insufficient funding are forcing clinicians to focus on more cost-effective solutions to this problem – the prevention and treatment of osteoporosis. Osteomodifying agents are widely used by physicians of various specialties. Bisphosphonates effectively reduce the risk of low-traumatic fractures against the background of an increase in bone mineral density. The level of effectiveness of bisphosphonates depends on the patient’s adherence to antiresorptive therapy and the degree of compensation for vitamin D and serum calcium. Low adherence to osteoporosis therapy is based on the need for long-term use of bisphosphonates and a different spectrum of adverse events. In the article, using alendronate as an example, the problem of low adherence to antiresorptive therapy will be considered and ways to solve it are presented.

Osteonecrosis of the jaw and antiresorptive agents in benign and malignant diseases: a critical review organized by ECTS

Context Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases. Osteonecrosis of the jaw (ONJ) is a rare, but severe condition, manifested as necrotic bone lesion(-s) of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed as Medication Related ONJ (MRONJ). Methods A working group of the European Calcified Tissue Society (ECTS) and two experts performed an updated detailed review of existing literature on MRONJ incidence, characteristics, and treatment applied in bone diseases with variable severity of skeletal insult, ranging from osteoporosis to prevention of cancer treatment-induced bone loss and SREs in cancer patients with bone metastases. We aimed to identify the differences in various aspects of MRONJ among these distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in each one of them. Results The risk for MRONJ is much higher in patients with advanced malignancies compared to those with benign bone diseases, because of the higher doses and more frequent administration of antiresorptive agents in individuals with compromised general health, along with co-administration of other medications that predispose to MRONJ. The overall risk for MRONJ is considerably lower than the benefits in all categories of patients. Conclusions The risk for MRONJ largely depends on the underlying bone disease and the relevant antiresorptive regimen applied. Physicians and dentists should keep in mind that the benefits of antiresorptive therapy far outweigh the risk for MRONJ development.

Influence of Preventive Tooth Extractions on Quality of Life in Patients with Antiresorptive Intake—A Prospective Longitudinal Study

Background: To find out whether preventive tooth extractions in patients on antiresorptive therapy have a direct impact on the patients’ overall quality of life (QoL); Methods: QoL using the five-level version of the EuroQol Group’s EQ-5D instrument (EQ-5D-5L) was longitudinally assessed in N = 114 prospectively enrolled patients with indication of preventive tooth extraction over a period of 12 months. Patients were stratified as high-risk (malignant disease with bone metastasis or multiple myeloma, with monthly high-dose antiresorptive therapy delivered intravenously [bisphosphonate] or subcutaneously [denosumab]) and low-risk/osteoporosis patients (weekly low-dose antiresorptive therapy administered orally [bisphosphonate] or half-yearly subcutaneously [denosumab]). The measurement time points were 4 weeks preoperatively (T0), 2 months (T1) and 1 year postoperatively (T2), respectively. Results: EQ-5D-5L index scores fell in a range from −0.21 to 1.00 in the low-risk group to 0.15 to 1.00 in the high-risk group. The t-test comparing the baseline index scores of both groups showed EQ-5D-5L index score in the low-risk group (0.708 ± 0.292) to be significantly smaller (p = 0.037) than in the high-risk group (0.807 ± 0.19). ANCOVA showed no significant differences in EQ-5D-5L index scores between the groups at T1 and T2. Conclusions: Preventive tooth extractions in patients undergoing antiresorptive treatment have no negative effect on QoL. Therefore, if indicated, preventive tooth extraction should not be omitted. Patient-oriented outcome measures are important to obtain a good risk–benefit balance for patient-specific treatment.

Evaluation of Preventive Treatment Protocols for Patients under Antiresorptive Therapy Undergoing Tooth Extraction at a Swiss University Clinic

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a dreaded complication in patients with compromised bone metabolism. The purpose of the present study was to examine the occurrence of ARONJ and its related factors among patients with a history of antiresorptive therapy undergoing tooth extraction using preventive protocols at a Swiss university clinic. Data were retrospectively pooled from health records of patients having received a surgical tooth extraction between January 2015 and April 2020 in the Clinic of Cranio-Maxillofacial and Oral surgery, University of Zurich. A total of 970 patients received an extraction with flap elevation or wound closure during this period. A total of 104 patients could be included in the study. Furthermore, variables including age, gender, smoking, risk profile, choice, indication and duration of antiresorptive therapy, number of extractions, extraction site, surgical technique, choice and duration of antibiotics as well as the presence of postoperative inflammatory complications were assessed. Overall, 4 patients developed ARONJ (incidence of 3.8%) after tooth extraction at the same location, without previous signs of osteonecrosis. Preventive methods included predominantly primary wound closure using a full thickness mucoperiosteal flap and prolonged perioperative antibiotic prophylaxis. In accordance with current literature, the applied protocol showed a reliable outcome in preventing ARONJ when a tooth extraction is required.

Review of Myeloma Therapies and Their Potential for Oral and Maxillofacial Side Effects

Myeloma is a common haematological malignancy in which adverse skeletal related events are frequently seen. Over recent years, treatment for myeloma has evolved leading to improved survival. Antiresorptive therapy is an important adjunct therapy to reduce the risk of bone fractures and to improve the quality of life for myeloma patients; however, this has the potential for unwanted side effects in the oral cavity and maxillofacial region. Osteonecrosis of the jaw related to antiresorptive medications and other myeloma therapies is not uncommon. This review serves to highlight the risk of osteonecrosis of the jaw for myeloma patients, with some suggestions for prevention and management.

Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia

Summary Hypophosphatasia (HPP) is a rare and under-recognised genetic defect in bone mineralisation. Patients presenting with fragility fractures may be mistakenly diagnosed as having osteoporosis and prescribed antiresorptive therapy, a treatment which may increase fracture risk. Adult-onset HPPhypophosphatasia was identified in a 40-year-old woman who presented with bilateral atypical femoral fractures after 4 years of denosumab therapy. A low serum alkaline phosphatase (ALP) and increased serum vitamin B6 level signalled the diagnosis, which was later confirmed by identification of two recessive mutations of the ALPL gene. The patient was treated with teriparatide given the unavailability of ALP enzyme-replacement therapy (asfotase alfa). Fracture healing occurred, but impaired mobility persisted. HPP predisposes to atypical femoral fracture (AFF) during antiresorptive therapy; hence, bisphosphonates and denosumab are contraindicated in this condition. Screening patients with fracture or ‘osteoporosis’ to identify a low ALP level is recommended. Learning points Hypophosphatasia (HPP) is a rare and under-recognised cause of bone fragility produced by impaired matrix mineralisation that can be misdiagnosed as a fragility fracture due to age-related bone loss. Antiresorptive therapy is contraindicated in HPP. Low serum alkaline phosphatase (ALP) provides a clue to the diagnosis. Elevated serum vitamin B6 (an ALP substrate) is indicative of HPP, while identification of a mutation in the ALPL gene is confirmatory. Enzyme therapy with recombinant ALP (asfotase alfa) is currently prohibitively costly. Treatment with anabolic bone agents such as teriparatide has been reported, but whether normally mineralized bone is formed requires further study.

▼Romosozumab for osteoporosis

Generic name: RomosozumabBrand name: EvenityFormulation: 105 mg solution for injection in a pre-filled penMarket Authorisation holder: UCB Pharma LimitedIndication: treatment of severe osteoporosis in postmenopausal women at high risk of fractureDose: 210 mg romosozumab (administered as two subcutaneous injections of 105 mg each) once a month for 12 months. It is recommended that patients begin antiresorptive therapy after completing treatment with romosozumab.Cost: £427.75 for two pre-filled pens each containing 105 mg romosozumabClassification: Prescription only medicine (POM) subject to additional monitoring (▼)

Multiple rebound-associated vertebral fractures after denosumab discontinuation: is prompt antiresorptive therapy always recommended, even when the risk of fracture seems low? A case report

Background: Non-osteoporotic patients with endocrine-sensitive breast cancer are often treated with denosumab only during the anti-aromatase treatment, and when the anti-aromatase therapy is discontinued, no antiresorptive drug is prescribed. This case report clearly shows how even a patient with a low risk of fractures could have multiple rebound vertebral fractures after denosumab discontinuation. Case Presentation: We report the case of a 60-year-old woman who suffered from multiple vertebral fractures only seven months after discontinuation of denosumab that had been administered to prevent bone loss related to three years of aromatase inhibitors as adjuvant therapy for breast cancer. No antiresorptive therapy was prescribed at the time of denosumab discontinuation, assuming that the patient had a low absolute risk of fracture after the withdrawal of the aromatase inhibitor. Conclusion: This case underlines the relative irrelevance of bone mineral density and clinical algorithms in predicting the risk of rebound-associated vertebral fractures after denosumab discontinuation and the strong recommendation to always switch to another antiresorptive therapy (such as zoledronic acid) immediately at the time of denosumab discontinuation.