Bisphosphonate Treatment Research Articles

Results of bisphosphonate withdrawal: duration of antiresorptive activity, fractures, changes in BMD and bone turnover markers

The review discusses the possibility of discontinuation of bisphosphonates (BPs), based on the mechanism of action of the drugs, the duration of their antiresorptive activity, criteria for discontinuation and return to therapy. BPs have a unique feature – maintaining the clinical effect for a long time after their withdrawal. Since BPs therapy is carried out for a long time, their accumulation in bone tissue, on the one hand, and the risk of developing severe adverse events, on the other hand, gave rise to discussion on the concept of temporary withdrawal of drugs and the organization of «drug holidays». The main criteria that are relied upon in the question of discontinuation of BPs and re-prescription at present are: 1) the risk of developing new fractures, 2) changes in bone mineral density (BMD), 3) dynamics of markers of bone metabolism. The conducted studies suggest that the suspension of treatment after 3-5 years of continuous therapy with BPs is possible in women who do not have low BMD indicators at the end of the course of therapy, while with continuing low levels of BMD, additional benefits from continuing therapy are likely. The loss of bone mass in the proximal femur and its preservation in the spine 2 years after discontinuation of BPs treatment is explained by their different localization and longer-term effect on bone metabolism in the spongy bone, i.e. in the spine. Delivery and absorption of BPs in the spine may be more intense than in other parts of the skeleton. Tracking the level of markers during a break in the treatment of BPs can be useful to determine the time of resumption of therapy: if their concentration approaches the baseline (before treatment), the patient’s condition should be reassessed and the issue of resuming therapy should be discussed. It should be noted that the optimal duration of «drug holidays» has not been established and should be selected individually depending on clinical circumstances, taking into account the presence of fractures, a significant decrease in BMD or an increase in markers of bone metabolism, as well as the presence and/or appearance of new clinically significant risk factors.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Comparison of bone mineral density of osteoporotic and osteopenia menopausal women treated with oral bisphosphonates before stopping the treatment and 1year after drug holiday period.

Osteoporosis is a skeletal and bone disorder characterized by bone fractures and decreased bone mineral density (BMD). Bisphosphonates have a great tendency to bind to minerals, and their long-term use can increase the risk of bone fragility in patients. Stopping bisphosphonates after a period of time is called a drug holiday (DH). Recent evidence has shown that patients' BMD may decrease again during DH. However, few studies have been done in this regard. In the present study, we compared the BMD of postmenopausal women during bisphosphonates treatment and 1year after DH. A total of 202 patients were selected with osteopenia (n = 95) and osteoporosis (n = 107); they had been treated with alendronate for 5years (a rheumatologist confirmed the diagnosis of osteopenia and osteoporosis) and had undergone DH for 1year. At the arrival of all patients, BMD was checked with the DXA (dual-energy X-ray absorptiometry) method using the 2007 American Explorer model Hologic device based on the Caucasian race. One year later, patients were reassessed for BMD by the same device. The analysis of femoral neck (FN) and lumbar spine (LS) T-score indices in the osteopenia and the osteoporosis groups showed reduction after DH, and the difference was statistically significant in both groups (p = 0.001). After 1year of stopping bisphosphonate treatment, the average of FN and LS BMD decreased in both groups (p = 0.001). In general, it can be said that DH can reduce FN and LS T-scores. The results indicated a significant reduction in BMD after the DH period for both the osteoporosis and osteopenia groups in the early months. Also, the effect of DH in osteoporosis patients was more compared to the osteopenia individuals, which could have implications for their treatment approach, and also its effect on bone health. Key Points • The DH can reduce FN and LS T-scores • The BMD reduced after the DH period for both the osteoporosis and osteopenia groups • After 1 year of stopping bisphosphonate treatment, the average of FN and LS BMD decreased in both groups.

Bisphosphonate treatment for skeletal complications in paediatric cancer-Experience from a single tertiary centre.

The aim was to analyse the use and safety of bisphosphonate treatment for metabolic bone complications in paediatric cancer patients. We retrospectively describe our experience with bisphosphonate treatment in 25 childhood cancer patients (aged <18 years) in a single tertiary hospital between 1999 and 2020. The most common primary diagnosis was acute lymphoblastic leukaemia (n = 16) and Hodgkin lymphoma (n = 3). Eleven patients (44%) had received allogeneic stem cell transplantation and two patients autologous stem cell transplantation. Sixteen patients (64%) had been treated with radiotherapy, either total-body (n = 11) or local (n = 5). The main indication for bisphosphonates was osteoporosis with vertebral compression fractures in 13/25, osteonecrosis in 6/25 and hypercalcaemia in 2/25. The bisphosphonate treatment was started on average 13 (range 0-76) months after the diagnosis of the bone complication. Bisphosphonate treatment lasted between weeks (hypercalcaemia) to 5 years (severe osteoporosis). Mild, non-symptomatic hypophosphatemia (n = 8), hypocalcaemia (n = 6) and moderate, transient pain (n = 6) were the most common adverse effects. No severe side effects were observed even when bisphosphonates were administered concomitantly with chemotherapy. Bone mineral density significantly improved with the bisphosphonate treatment (mean lumbar spine Z-score -1.17 vs. -0.07, p < 0.001). Bisphosphonate treatment was well tolerated in this paediatric patient cohort.

Oral health, dental treatment, and medication related osteonecrosis of the jaw in multiple myeloma – a longitudinal cohort study

ObjectiveThe objective of the present study was to investigate oral health status, oral health related quality of life, and identify risk factors associated with invasive dental treatment and medication related osteonecrosis of the jaw in patients with multiple myeloma.Material and methodsPatients newly diagnosed with multiple myeloma (n = 144) referred between January 2015 and September 2022 were retrospectively included. The patients underwent a thorough clinical and radiological oral examination and odontogenic infections were treated before the start of bisphosphonate treatment. The patients were followed annually, including clinical and radiological examinations. The oral health related quality of life was investigated by the OHIP-14 questionnaire.ResultsDental treatment (RR = 7.75), receiving combination antineoplastic therapy≥3 (RR =4.13), periodontitis (RR = 4.21), and reduced number of teeth (RR = 2.87) were associated with an increased risk of medication related osteonecrosis of the jaw. The response rate of the OHIP-14 questionnaire was 70.2%. Oral pain or discomfort in the mouth related to the medical treatment was reported by 30.5%.ConclusionDental screening and treatment planning in patients with Multiple Myeloma may result in fewer oral infections and fewer interruptions of the medical treatment of myeloma.

Differences in bone histomorphometry between White postmenopausal women with and without atypical femoral fracture after long-term bisphosphonate therapy.

Bone histomorphometric endpoints in transilial biopsies may be associated with an increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BPs). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time-matched patients who either had AFF or did not have AFF. In this study, we performed transiliac bone biopsies in 52 White postmenopausal women with (n= 20) and without (n= 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4-17yr. Despite the matched range of treatment duration (4-17yr), AFF patients received alendronate for significantly longer time (10.7yr) than non-AFF patients (8.0yr) (P= .014). Bone histomorphometric endpoints reflecting microstructure and turnover were assessed in cancellous, intracortical, and endocortical envelopes from transilial biopsy specimens obtained from BP-treated patients 3-6mo after AFF and from non-AFF patients with similar age-, gender-, and range of BP treatment duration. However, in both cancellous and intracortical envelopes, AFF patients had significantly lower wall thickness (W.Th) and higher osteoclast surface (Oc.S/BS) than non-AFF patients. In addition, AFF patients had significantly higher eroded surface (ES/BS) only in the intracortical envelope. None of the dynamic variables related to bone formation and turnover differed significantly between the groups. In conclusion, in the ilium of BP-treated patients with osteoporosis, AFF patients have lower thickness of superficial bone (lower W.Th) of the cancellous and cortical envelopes than non-AFF patients. AFF and non-AFF patients have a similar bone turnover rate in the ilium. Furthermore, in this population, as in previous work, AFF is more likely to occur in BP-treated patients with longer treatment duration.

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis

BackgroundTeriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment.MethodsIn this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months.ResultsTwelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and β-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment.ConclusionOur results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

Bisphosphonate therapy in the management of diffuse sclerosing osteomyelitis of the mandible: a systematic review and narrative synthesis

Background: Diffuse sclerosing osteomyelitis (DSO) affecting the mandible is an uncommon condition characterised by recurrent pain and functional disturbances. Traditional treatments involving antibiotics, steroids, and analgesics have generally yielded unsatisfactory results. Numerous articles have proposed the utilisation of bisphosphonate therapy as an alternative approach to achieve sustained symptom relief. This study aims to consolidate the available evidence on the effectiveness of bisphosphonate therapy in managing DSO. Methods: A systematic review protocol was registered with PROSPERO and reported in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses. Comprehensive electronic search strategies were devised, and studies were screened based on predefined inclusion and exclusion criteria. Results: Ten articles met the eligibility criteria, encompassing a total of 135 patients diagnosed with DSO who received bisphosphonate treatment. All included studies consistently reported a reduction in pain levels and swelling, along with a decrease in the cumulative use of analgesics. The majority of patients reported long-lasting symptom improvement with bisphosphonate therapy. Notably, four studies documented improvements in maximal mouth opening, with one study reporting a mean increase of 9.6mm. Furthermore, six studies observed improvements in panoramic radiographs and cone beam computed tomography scans, with one publication describing two patients exhibiting near-normal bone architecture. Importantly, all studies reported the absence of long-term complications. Conclusions: Bisphosphonate therapy emerges as a promising treatment modality for DSO, exhibiting efficacy in symptom alleviation and radiological enhancement while conferring lasting benefits. Nevertheless, further prospective studies are warranted to refine treatment protocols and substantiate these findings.

Assessing bone formation on hydrophilic and hydrophobic implant surfaces in a murine model treated with bisphosphonates.

To evaluate the osseointegration of implants with hydrophobic (HFB) and hydrophilic (HFL) surfaces in a murine model of high-dose bisphosphonates (BPs). Sixty-four rats were randomly allocated into four groups: control group with HFB implants (CG-HFB), control group with HFL implants (CG-HFL), BP group with HFB implants (BP-HFB), and BP group with HFL implants (BP-HFL). Animals were euthanized after 15 and 45 days (n=8). The dependent variables assessed were the removal torque (biomechanical analysis), the bone volume around the implants (%BV/TV) (microtomographic analysis), the bone-implant contact (%BIC), the bone between the threads (%BBT) (histomorphometric analysis), and the expression of bone metabolism markers (immunohistochemistry analysis). The CG-HFL and BP-HFL groups presented higher removal torque than the CG-HFB and BP-HFB implants. The %BIC of the CG-HFL surfaces was slightly higher than that of the CG-HFB implants. The BP-HFB and BP-HFL groups presented a higher %BIC than that of the CG-HFB and CG-HFL groups (p<0.001). BP therapy also increased the %BBT at both implant surfaces. Higher levels of ALP were observed in the matrix region of bone tissue on the HFL surfaces than on the HFB surfaces. Both surfaces enable osseointegration in rats under BP therapy. The study demonstrates that hydrophobic (HFB) and hydrophilic (HFL) implant surfaces can promote osseointegration in rats undergoing bisphosphonate therapy. The HFL surfaces exhibited improved biomechanical performance, higher bone-implant contact, and increased bone volume, suggesting their potential clinical relevance for implant success in individuals on bisphosphonate treatment.

Bisphosphonate Use and Risk of Atypical Femoral Fractures: A Danish Case-Cohort Study With Blinded Radiographic Review.

Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined. This population-based case-cohort study utilized data from the Danish National Healthcare system, including longitudinal records of medication use, healthcare utilization, and x-ray images. Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010 and 2015 (n = 4973) were identified and compared to a random sample (n = 37 021). Bisphosphonate use was collected from 1995-2015. Fracture radiographs (n = 4769) were reviewed by blinded study radiologists to identify AFFs (n = 189) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10. Compared to <1 year of BP use, 5 to 7 years of use was associated with a 7-fold increase in AFF (adjusted HR = 7.29 [CI: 3.07, 17.30]); the risk of AFF fell quickly after discontinuation. The 5-year number needed to harm for one AFF was 1424, while the 5-year number needed to treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure. The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.

Effect of anti-resorptive therapy on implant failure: a systematic review and meta-analysis.

This review was conducted to systematically assess the impact of bisphosphonates (BPs) and denosumab, used as anti-resorptive therapies, on the incidence of dental implant failure. Electronic and manual searches were performed in accordance with the described search protocol. Only articles that met the inclusion criteria were selected. The primary outcome was implant failure, while secondary outcomes included biological complications and comorbidities. Following data extraction, a quality assessment and meta-analysis were conducted. Fourteen eligible studies were included in the analysis following a qualitative evaluation. BP administration, regardless of the timing of anti-resorptive therapy, did not significantly increase the risk of implant failure (odds ratio [OR], 1.40; 95% confidence interval, 0.83-2.34). Subgroup analysis revealed a slightly higher, although statistically insignificant, risk of failure in patients with a follow-up period of 3 years or more compared to those with a follow-up duration of less than 3 years (with ORs of 2.82 and 1.53, respectively). Due to a lack of eligible studies, a meta-analysis for denosumab could not be conducted. Our findings suggest that BP treatment does not compromise the survival of dental implants. Specifically, in patients with osteoporosis, implant failure rates were not significantly influenced by the administration of BPs before the placement of dental implants, suggesting that low-dose BP therapy may not contraindicate implant placement. Nevertheless, regular check-ups and maintenance periodontal treatment must not be neglected, and concomitant biological factors should be considered to ensure the long-term success of implant rehabilitation.

Bone manifestations in Snyder‐Robinson syndrome

PurposeSnyder-Robinson syndrome (SRS) is a rare, X-linked condition caused by loss of function variants in the SMS gene, which codes for spermine synthase, an enzyme essential for synthesis of the polyamine spermine [1]. It is speculated that polyamines are crucial for osteoblast activity [2]. While published cases of SRS have reported osteopenia or osteoporosis, the natural history of bone health in individuals with SRS has not yet been explored. It is hypothesized that the natural history of bone health in these individuals results in low bone density for age and increased fractures in the absence of intervention. It is important for healthcare providers to recognize bone manifestations in individuals with SRS so that an appropriate standard of care can be administered. MethodsCase histories of 40 males with SRS spanning various ages from birth through adulthood were obtained from the Global Snyder-Robinson Syndrome Natural History Study and previously published cases. The data described and summarized in this study included dual x-ray absorptiometry (DEXA) scan results, fractures, and bisphosphonate treatment histories. ResultsMost individuals experienced at least one fracture, which was most common in their lower extremities. A greater number of fractures was reported when individuals did not receive bisphosphonates. Favorable DEXA results showed improvements in Z-scores and bone mineral density in individuals on bisphosphonates. ConclusionSRS is associated with persistent low bone density for age or osteoporosis. Treatment with bisphosphonates and long-term use requires further evaluation. This review contributes to the knowledge of bone health in the SRS population.

Imaging aspects of maxillomandibular bone alterations in patients with multiple myeloma treated with bisphosphonates: A systematic review.

Multiple myeloma (MM) is a rare cancer that is typically managed with bisphosphonates to slow bone resorption and prevent skeletal complications. This study aimed to identify imaging patterns in MM patients receiving bisphosphonate therapy. This systematic review included studies investigating maxillomandibular bone alterations based on imaging examinations in MM patients treated with bisphosphonates. The selected studies were qualitatively assessed using the Critical Appraisal Tools from SUMARI. Six studies, involving 669 MM patients, were included, with 447 receiving bisphosphonate treatment. The majority were treated with pamidronate, zoledronate, or a combination of both. Seventy patients developed medication-related osteonecrosis of the jaw (MRONJ), predominantly in the mandible, characterized by the presence of bony sequestrum, bone sclerosis, increased periodontal ligament space, osteolytic lesions, and osteomyelitis as observed in imaging analyses. For non-MRONJ lesions, the mandible also exhibited the highest frequency of asymptomatic bone alterations. These ranged from "punched-out" osteolytic lesions or "soap bubble" lesions to solitary bone lesions, areas of bone sclerosis, abnormalities of the hard palate, osteoporosis, non-healed alveoli, and cortical bone rupture. MM patients treated with bisphosphonates display radiographic patterns of maxillomandibular bone lesions. These patterns aid in diagnosis and facilitate early and targeted treatment, thereby contributing to improved morbidity outcomes for these patients.

The efficacy of bisphosphonates for osteoporosis in young Cushing's disease patients with biochemical remission: a retrospective cohort study.

Patients with Cushing's disease (CD) often experience slow recovery of bone mineral density (BMD), and the effectiveness of anti-osteoporosis drugs in young CD patients who have achieved biochemical remission after surgery is not well understood. Therefore, we aimed to explore whether bisphosphonates could help accelerate the recovery of osteoporosis in young CD patients with remission. We retrospectively enrolled 34 young patients with CD who achieved postoperative biochemical remission. All patients suffered from osteoporosis before surgery and were divided into postoperative bisphosphonate treatment group (16 cases) and without bisphosphonate treatment group (18 cases). Clinical data, BMD (Z Value), and bone turnover markers were collected at the time of diagnosis and one year after successful tumor resection. The Z values in the lumbar spine showed slight improvement in both groups at follow-up compared to baseline, but this improvement was not statistically significant. There was no significant difference observed between the two groups at follow-up. One year after operation, bone formation markers (OC and P1NP) were significantly higher than those at baseline in both groups. However, OC and P1NP in the bisphosphonate treatment group were lower than those in control group at one year follow-up. In without bisphosphonate treatment group, β-CTX from follow-up visit was higher than that at baseline, while no significant difference was observed in the bisphosphonate treatment group before and after surgery. Young patients with Cushing's disease combined with osteoporosis might not benefit from bisphosphonate therapy for osteoporosis recovery in the first year after achieving biochemical remission.

Is Teriparatide Superior in Treating Osteoporotic Vertebral Compression Fractures in Comparison to Bisphosphonates Treatment Alone: A 2-Year Retrospective Analysis.

Retrospective cohort study. This study aimed to compare the efficacy of bisphosphonates and teriparatide in the management of osteoporotic vertebral compression fractures with regard to pain management, prevention of nonunion, and radiological as well as clinical outcomes. Osteoporosis refers to a skeletal disorder characterized by decreased bone strength caused by poor bone density and quality causing fragility, resulting in long periods of pain-related immobilization. In a 24-month follow-up retrospective study, 191 patients with osteoporotic vertebral compression fractures were randomly assigned to the bisphosphonate group (n=104) or the teriparatide group (n=87), with patients opting for their treatment between January 2016 and October 2020. Demographic data and patient-reported outcomes scores, including the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), union rates, and kyphosis progression, were assessed at baseline, 6 months, 1 year, and 2 years after treatment. Both groups had a significant decrease in VAS, from 8.38±0.74 to 3.15±1.40 in the bisphosphonate group and from 8.49±0.73 to 1.11±0.31 in the teriparatide group. The ODI scores reduced significantly at 2-year follow-ups, recording 25.02±13.94 and 15.11±2.17 in the bisphosphonate and teriparatide groups, respectively. Risks of nonunion development were slightly higher at 11.53% in the bisphosphonate group and 8.63% in the teriparatide group required operative intervention. The kyphosis progression angles were also significantly lower in the teriparatide group (4.97°±0.78°) than in the bisphosphonate group (8.09°±1.25°). Over time, numerous studies have demonstrated the efficacy of bisphosphonates and teriparatide in ameliorating pain. In this study, the efficacy of teriparatide surpassed that of bisphosphonates in certain aspects, such as the initial 6-month union rates and reduction in the progression of segmental kyphosis. However, bisphosphonates and teriparatide yield similar and favorable union rates at 1 year and final follow-up.

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13&nbsp;years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10months to 2years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Position Statement: Postmenopausal Osteoporosis Treatment Strategies in Korea

Classifying patients with osteoporosis according to fracture risk and establishing adequate treatment strategies is crucial to effectively treat osteoporosis. The Korean Society for Bone and Mineral Research has issued a position statement regarding appropriate treatment strategies for postmenopausal osteoporosis. According to previous fragility fracture history, bone mineral density (BMD) test results, fracture risk assessment tool, and several clinical risk factors, fracture risk groups are classified into low, moderate, high, and very-high-risk groups. In high-risk groups, bisphosphonates (BPs) and denosumab are recommended as first-line therapies. Sequential BP treatment after denosumab discontinuation is required to prevent the rebound phenomenon. In the very high-risk group, anabolic drugs (teriparatide or romosozumab) are recommended as a first-line therapy; sequential therapy with antiresorptive agents is required to maintain BMD gain and reduce fracture risk. Fracture risk was reassessed annually, and the treatment plan was determined based on the results, according to the osteoporosis treatment algorithm for fracture risk.

Clinical characteristics, densitometric parameters and outcomes of patients with atypical femoral fractures related to bisphosphonate treatment for osteoporosis.

We described the clinical and densitometric characteristics and treatment outcomes of patients who developed atypical femoral fractures (AFF) while on bisphosphonate for osteoporosis. We performed a retrospective cohort study including all adults aged ≥50 years who developed AFF while on bisphosphonates between 1 January 2008 and 31 December 2020, and subsequently managed in the Osteoporosis Centre at Queen Mary Hospital in Hong Kong. A control group of patients who developed fragility hip fractures while on bisphosphonates in the same period was included for comparison. We compared the clinical and densitometric characteristics between the two groups, and described the clinical outcomes for the AFF group. In total, 75 patients were included (AFF: n = 35; fragility hip fracture: n = 40). All were related to oral bisphosphonates. The AFF group was characterised by a longer duration of bisphosphonate use (median of 5 years), higher bone mineral density (BMD) and more acute neck-shaft angle (all p < 0.05). Following AFF, 8 patients (22.9%) did not receive any subsequent bone-active agents: due to refusal to use an injectable, or BMD out of osteoporotic range. Most of those who received bone-active agents were given teriparatide, followed by raloxifene, and achieved stable BMD. However, subsequent fragility risk remained high. Nonetheless, AFF did not confer excess morbidity and mortality. AFF was characterised by usually long duration of bisphosphonate use, higher BMD and more acute neck-shaft angle. AFF did not confer significant impairment in mobility or mortality. Nonetheless, further research work is necessary to optimise bone health among patients who develop AFF.

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

THU453 Chronic Headaches As A Presentation For Monostotic Craniofacial Fibrous Dysplasia: A Case Study

Abstract Disclosure: B. Dyer: None. R.K. Bhattacharya: None. Background: Monostotic craniofacial fibrous dysplasia (CFFD) is often asymptomatic and is found incidentally on imaging. Previous reports described cases in which CFFD diagnosis was preceded by chronic headaches, but there remains a lack of clinical association between these diagnoses. Clinical Case: Patient is a 22-year-old female with a long history of chronic headaches who presented to the emergency department two days after a motor vehicle accident with complaints of headache, blurred vision, nausea, and dizziness. CT revealed an incidental sclerotic mass in the left frontal region measuring 7.9x7.3x3.7cm extending inferiorly into the left ethmoid sinus. At her primary care follow-up, she reported a pounding, left-sided headache in addition to balance issues, dizziness, nausea, and blurry vision. Workup was significant for vitamin D level of 11.2ng/mL (n = 30-100ng/mL), alkaline phosphate of 106U/L (n = 35-104U/L), and calcium of 9.1mg/dL (n = 8.6-10.3mg/dL). MRI was significant for a heterogeneous, hypointense expansile calvarial lesion within the left frontal and left sphenoid bones. The patient was diagnosed with CFFD based on radiologic findings. The patient was advised against surgical intervention due to her disease’s large, invasive nature. The patient was seen by neurology for recurrent headaches and was subsequently started on topiramate with partial symptom relief. Endocrinologist management included confirmation of monostotic CFFD by bone scan. Biopsy was deferred due to the low likelihood of malignant transformation, and bisphosphonate treatment was initiated. She was subsequently started on 5000 IU per day of vitamin D to normalize the vitamin D level before the initiation of bisphosphonate treatment for her pain. She received 5mg intravenous infusion of zoledronic treatment. At follow-up, the patient states she had significant improvement in all symptoms. Conclusion: Pain from FD can be debilitating and often increases in severity as the patient ages, though pain is not strongly correlated to presentation or disease burden. The mechanism by which CFFD produces pain is not fully elucidated. The unique innervation of bone and the creation of new sensory nerve fibers during inflammatory states may contribute. Additionally, excess IL-6 during inflammatory states may also play a role in pain production due to lesion expansion from osteoclast activation, cystic formation within the lesion, and hormonal reactivity of the lesion. Bisphosphonates are believed to inhibit IL-6 production, reducing osteoclastic activity and leading to symptomatic pain relief. In the case presented, the patient’s chronic headaches improved significantly following combination therapy with migraine abortive medication and bisphosphonate therapy. Early recognition and multidisciplinary treatment are key in the long-term management of CFFD pain. Presentation: Thursday, June 15, 2023