Fosamax Fractures-Justice Has Not Been Served.

This Viewpoint discusses the ongoing lawsuit between plaintiffs who had been affected by atypical femoral fractures while receiving alendronate and the drug manufacturer.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Avoiding complications in percutaneous osteoplasty.

Percutaneous osteoplasty techniques include cement injection either solely performed or in combination to hardware such as cannulated screws, peek implants or other metallic hardware including micro-needles and Kirschner wires. Depending on bone and local forces applied, fracture and osseous defect characteristics as well as symptoms and operator's preference percutaneous osteoplasty techniques include cementoplasty, fixation by internal cemented screw and augmented osteoplasty. Literature data support efficacy and safety of these techniques, focusing mainly on the minimal invasive nature of these approaches along with minimum overall morbidity and mortality and an impressive pain reduction effect. Percutaneous osteoplasty techniques in the peripheral skeleton are indicated for pain palliation or for prevention of impeding pathologic fractures. Although safe, osteoplasty techniques are not without risk of complications and adverse events. Complications are classified based either upon clinical impact or timing of occurrence; complications' reviewing and grading should be performed on terms of a uniform and accurate reproducible and validated categorization system. Significant factors for avoiding complications in percutaneous osteoplasty techniques include proper training, patient- and lesion-tailored approach, high-quality imaging guidance, sterility as well as appropriate selection of technique and materials. The present article reports the possible complications of percutaneous osteoplasty techniques and reviews the prerequisites necessary for avoiding and managing these adverse events.

An unusual case of bone regeneration of a necrotic mandible with pathologic fracture in an elderly hemodialysis patient with medication-related osteonecrosis of the jaw: a case report and review of the literature.

BACKGROUND: Bisphosphonates are frequently used for osteoporosis. Medication-related osteonecrosis of the jaw, a complication of bone-modifying agents, including bisphosphonates or angiogenic inhibitors, can be challenging to treat in elderly patients with numerous preexisting conditions. Achieving good treatment outcomes is especially difficult in patients with pathological fractures accompanied with extraoral fistulae. CASE PRESENTATION: We report an unusual case of prominent bone regeneration following palliative surgical treatment in a 72-year-old Japanese female patient undergoing hemodialysis. She previously had severe osteoporosis due to renal osteodystrophy and was receiving antiresorptive intravenous bisphosphonate. Computed tomography revealed a discontinuous left lower mandibular margin with a pathologic fracture and extensive, morphologically irregular sequestrum formation (80 × 35 × 20 mm). The patient was diagnosed with stage III medication-related osteonecrosis of the jaw and pathologic mandibular fracture. Immediately before the surgery, the anticoagulant used for dialysis was changed from heparin to nafamostat mesylate to reduce the risk of intraoperative bleeding. Sequestrectomy was performed under general anesthesia. Postoperative infection was not observed, the intraoral and submandibular fistula disappeared, and, surprisingly, prominent spontaneous bone regeneration was observed postoperatively at 6 months. Despite the severe systemic condition of the patient, the conservative surgical approach with sequestrectomy has yielded desirable results for more than 6 years since the surgery. CONCLUSIONS: This rare report of spontaneous bone regeneration in a patient of advanced age and poor general condition is the oldest case of mandibular regeneration ever reported.

Retrospective evaluation of pathologic fractures in medication related osteonecrosis of the jaw.

The aim of this study was to focus on the MRONJ-related pathologic fractures, their incidence, and to analyze possible causative factors for their occurrence. Pathologic fracture in patients suffering frm MRONJ were identified, examined in detail, and the patient characteristics were evaluated. In 116 patients (73 female and 43 male; mean age 62.08 ± 13.6 years), pathologic fracture incidence was found to be 4.31%. Zoledronic acid was the most commonly used anti-resorptive drug (77.8%). Median antiresorptive usage was 24 months. Five patients had pathologic fractures in the mandible. Four fracture patients had metastatic prostate cancer, and one had metastatic renal cell cancer. This case series study can provide clinical insight into which factors are associated with pathologic fractures. Cancer type, medical comorbidities, additive toxicity of the combination of antiresorptive and antiangiogenic drugs, specific pathogens, and dento-alveolar surgical procedures may be some of the important factors that need to be considered. Since MRONJ-related pathologic fracture management can be complicated, it may be good to focus on the causative factors and prevent occurrence with regular follow-up as often as possible in line with these factors.

Corticosteroids and bone health in people with asthma: A systematic review and meta-analysis.

BACKGROUND: Understanding the potential deleterious effects of corticosteroids on bone health in people with asthma is important when making treatment decisions. There is a need for clearer evidence to better quantify the risk and effect size. METHODS: Databases were systematically searched to identify studies reporting on bone mineral density (BMD) measurement and risk of osteoporosis or fracture, comparing people with asthma exposed to inhaled (ICS) or oral (OCS) corticosteroids, with nonexposed people with asthma and healthy controls. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method. RESULTS: This review consists of 28 studies (six randomized control trials and 22 observational). There was no effect of ICS on bone loss both at spine and femoral neck in asthma. People with asthma receiving OCS were at greater risk of osteoporosis than nonexposed people with asthma (pooled HR = 1.76; 95%CI: 1.48 to 2.09; I2=68%). Similarly, higher ICS exposure was associated with higher risk of osteoporosis (OR = 1.63; 95%CI: 1.33 to 1.99) and fracture (pooled OR = 1.19; 95%CI: 1.05 to 1.35; I2=0%) when comparing people with asthma receiving ICS and not. CONCLUSION: Patients with asthma exposed to OCS or high ICS doses become more susceptible to bone comorbidities. Striking the right balance between efficacy and safety of steroids in asthma is important to improve patients' quality of life.

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

PURPOSE: No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons. MATERIALS AND METHODS: Individual patient data from the phase III ARAMIS trial (NPLACEBO=553; NDAROLUTAMIDE=943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (NPLACEBO=401; NAPALUTAMIDE=806) and PROSPER (NPLACEBO=468; NENZALUTAMIDE=933) trials. Only baseline factors consistently reported across trials were included as matching covariates. Both indirect comparisons matched on age, prostate specific antigen level and doubling time, Eastern Cooperative Oncology Group performance status, Gleason score, and bone-sparing agent use. Darolutamide vs apalutamide also matched on prior surgery and darolutamide vs enzalutamide also matched on region. Risk differences and odds ratios were calculated for adverse events and hazard ratios for metastasis-free survival. RESULTS: No differences in metastasis-free survival hazard ratios were found after matching in either comparison. However, fall, fracture and rash rates were statistically significantly lower in favor of darolutamide vs apalutamide. Fall, dizziness, mental impairment, fatigue and severe fatigue rates were statistically significantly lower in favor of darolutamide vs enzalutamide. CONCLUSIONS: While metastasis-free survival did not differ across drugs in these cross-trial indirect comparisons, darolutamide showed a favorable safety and tolerability profile in prespecified adverse events vs apalutamide and enzalutamide. Consideration of these adverse events is important in clinical decision-making and treatment selection in nonmetastatic castration-resistant prostate cancer.

Atypical femur fracture incidence in women increases with duration of bisphosphonate exposure.

In a northern California population of older women who were treated with oral bisphosphonate drugs, the incidence of atypical femur fracture, a rare complication of treatment, increased with longer duration of bisphosphonate exposure. These findings align with those previously reported in an independent southern California population. INTRODUCTION: The age-adjusted incidence of atypical femur fracture (AFF) reported in southern California increased with bisphosphonate (BP) exposure, ranging up to 113 per 100,000 person-years for 8-10-year exposure. This study examines the incidence of AFF in a northern California population. METHODS: Women age 45-89 years who initiated oral BP during 2002-2014 in Kaiser Permanente Northern California were followed for AFF outcome, defined by a primarily transverse diaphyseal femur fracture through both cortices, with focal periosteal/endosteal hypertrophy, minimal trauma, and minimal/no comminution. Total BP exposure was determined from dispensed prescriptions. The incidence of AFF, calculated for 2-year BP categories ranging from < 2 to > 10 years, was age-adjusted using the 2000 US Census. RESULTS: Among 94,542 women, 107 experienced an AFF during or < 1 year after BP cessation (mean exposure 6.6 ± 3.0 years and total days' supply 5.7 ± 2.8 years at AFF). A strong relationship between AFF incidence and increasing BP exposure was seen, more than doubling for each 2-year category until 8-10 years. Among women with 2- to < 4-year BP, the crude and age-adjusted incidence was 18 and 9 per 100,000 person-years but increased over 2- and 5-fold for women with 4- to < 6- and 6- to < 8-year BP, respectively. For those receiving ≥ 8-year BP, the crude and age-adjusted incidence peaked at 196 and 112 per 100,000 person-years exposure. CONCLUSION: Incidence of AFF increases markedly after 4-6 years of BP. These trends align with southern California and confirm a strong BP duration-related risk of this rare but serious event.

Antiresorptive-associated spontaneous fractures of both tibiae, followed by an atypical femur fracture during the sequential treatment with alendronate, denosumab then teriparatide.

A 35-year-old man with juvenile idiopathic arthritis since childhood presented with bilateral atypical tibial fractures, followed by a later, single atypical fracture of the femur. The fractures were associated with 6 years of oral alendronate treatment immediately followed by subcutaneous denosumab therapy and later teriparatide therapy for osteoporosis. Atypical fractures are known to occur in the femur following bisphosphonate therapy; however, there are only a few documented cases of atypical fractures in the tibia. Our case highlights a rare but serious complication of a commonly prescribed antiresorptive agent. It also shows that teriparatide, while helpful in increasing bone mass, does not fully prevent the development of atypical fractures. Careful investigation should be considered in patients on long-term antiresorptive therapy presenting with bony tenderness to exclude an atypical fracture.

Medications associated with fracture risk in patients with rheumatoid arthritis.

OBJECTIVE: To examine the fracture risk with use of disease-modifying antirheumatic drugs (DMARDs), statins, proton pump inhibitors (PPIs), opioids, non-opioid analgesics and psychotropic medications in a US-wide observational rheumatoid arthritis (RA) cohort. METHODS: Patients with RA without prior fracture from 2001 through 2017 in FORWARD, a longitudinal observational registry, were assessed for osteoporosis-related site fractures (vertebra, hip, forearm and humerus). DMARD exposure was assessed in four mutually exclusive groups: (1) methotrexate monotherapy-reference, (2) tumour necrosis factor-α inhibitors (TNFi), (3) non-TNFi biologics and (4) others. Non-DMARDs and glucocorticoids were classified as current/ever use and based on treatment duration. Fracture Risk Assessment Tool (FRAX) scores estimating for 10-year major osteoporotic fractures were calculated. Cox proportional hazard models stratified by FRAX were used to adjust for confounders. RESULTS: During median (IQR) 3.0 (1.5-6.0) years of follow-up in 11 412 patients, 914 fractures were observed. The adjusted models showed a significant fracture risk increase with use of any dose glucocorticoids ≥3 months (HR (95% CI) for <7.5 mg/day 1.26 (1.07 to 1.48) and for ≥7.5 mg/day 1.57 (1.27 to 1.94)), opioids (for weak: 1.37 (1.18 to 1.59); strong: 1.53 (1.24 to 1.88)) and selective serotonin reuptake inhibitors (SSRIs) (1.37 (1.15 to 1.63)). Fracture risk with opioids increased within 1 month of use (1.66 (1.36 to 2.04)) and with SSRIs >3 months of use (1.25 (1.01 to 1.55)). Statins (0.77 (0.62 to 0.96)) and TNFi (0.72 (0.54 to 0.97)) were associated with reduction in vertebral fracture risk only. PPIs and other psychotropic medications were not associated with increased fracture risk. CONCLUSION: Use of opioids, SSRIs and glucocorticoids were associated with increased risk of any fracture in patients with RA, whereas statins and TNFi were associated with decreased vertebral fractures.

Salvage of failed osteosynthesis for an atypical subtrochanteric femoral fracture associated with long-term bisphosphonate treatment using a 95° angled blade plate.

AIMS: The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment. PATIENTS AND METHODS: Between October 2008 and July 2016, 14 patients with failed osteosynthesis of an atypical subtrochanteric femoral fracture were treated with a blade plate (atypical group). Their mean age was 67.8 years (60 to 74); all were female. During the same period, 21 patients with failed osteosynthesis of a typical subtrochanteric fracture underwent restabilization using a blade plate (typical group). Outcome variables included the time of union, postoperative complications, Harris Hip Score, and Sanders functional rating scale. RESULTS: In the atypical group, union was achieved in 12 patients (85.7%) at a mean of 8.4 months (4 to 12). The mean follow-up was 31.2 months (12 to 92) The plate broke in one patient requiring further stabilization with a longer plate and strut-allograft. Another patient with failure of fixation and varus angulation at the fracture site declined further surgery. In the typical group, union was achieved in 18 patients (85.7%) at a mean of 7.9 months (4 to 12). There was no difference in the mean Harris Hip Score between the two groups (83.1 points vs 86.8 points; p = 0.522) at the time of final follow-up. Sanders functional rating scores were good or excellent in 78.6% of the atypical group and in 81.0% of the typical group. CONCLUSION: The 95° angled blade plate was shown to be an effective fixation modality for nonunion of atypical subtrochanteric fractures with a high rate of union and functional improvement, comparable to those after fractures not associated with bisphosphonate treatment. Cite this article: Bone Joint J 2018;100-B:1511-17.

Surgical Complications Associated With Atypical Femur Fractures Attributed to Bisphosphonate Use.

Complications of atypical femur fractures (AFFs) are common. AFFs often receive the same treatment as other femoral fractures; however, there appears to be a higher rate of adverse outcomes. Nine patients sustained a total of 13 AFFs, had documented bisphosphonate use before fracture, and had surgery between 2006 and 2012. Complications included continued pain, surgical revision, nonunion, malunion, deformity, or heterotopic ossification. The overall complication rate was 33.3%, with four of the 12 surgeries performed at this institution resulting in one nonunion and three minor complications. None of the primary fixations required revision. There was a higher complication rate for AFFs when compared with non-bisphosphonate-related intramedullary nail femur fracture fixations. This cohort demonstrated a lower rate of major complications compared to the literature. Using a reamed, statically locked nail, halting bisphosphonate medication, and allowing early weight bearing is a safe and efficacious method to treat atypical femur fractures. (Journal of Surgical Orthopaedic Advances 27(1):14-20, 2018).

A proposal for an atypical femur fracture treatment and prevention clinical practice guideline.

The prevention as well as the treatment of atypical femur fractures (AFFs) remains controversial but there have been many clinical recommendations suggested. We have summarized these recommendations as well as expanded upon them in this paper. INTRODUCTION: The purpose of the paper was to develop a clinical practice guideline that both treats AFF and decreases the risk of AFF in patients requiring antiresorptive medications. Examples of these medications include bisphosphonates and denosumab for the treatment of osteoporosis. METHODS: A literature review looking for recommendations on AFF identification, management, and prevention was done. We also performed an updated review of clinical guidelines on AFF prevention and treatment that were developed for the Kaiser Permanente osteoporosis/fracture prevention team. RESULTS: Concise clinical practice guidelines are presented that can be applied in treatment of AFF as well as help reduce the risk of developing an AFF in patients requiring antiresorptive medications. These guidelines are based on using both typical fracture and AFF risk assessment to determine duration of antiresorptive of 3 to 5 years before consideration if a drug holiday is needed. Specific groups such as younger Asian women should be reassessed at 3 years with DXA and FRAX to see if a drug holiday is needed whereas patients at higher risk for typical fractures may be reassessed at 5 years of treatment. The DXA rescreening can now be accessed if focal or generalized lateral cortex changes are present that may indicate incomplete AFFs are present. If an incomplete AFF is discovered either by DXA or by other imaging studies, it is imperative to stop antiresorptive medications and to take additional measures to lower the risk of progression to a complete AFF. If complete AFF does occur, then antiresorptive medications should be stopped and additional measures should be taken to decrease the risk of developing an AFF on the contralateral femur. CONCLUSIONS: Clinical practice guidelines for the treatment and prevention of AFF will benefit clinicians who are frequently faced with having to make clinical decisions in patients requiring antiresorptive medications.

[Subtrochanteric pathological fracture on bisphosphonates]. / Le cas clinique du mois. Fracture pathologique sous-trochantérienne sur prise de bisphosphonates.

Bisphosphonates have frequently shown their efficacy in the treatment of osteoporosis, including ibandronate and alendronate. But more and more mention is made in the literature of patients taking a long-term bisphosphonate and undergoing an atypical fracture associated with this therapy. These complications are most often femoral fractures in the proximal part of the femoral diaphysis. We report the case of a 73-year-old patient who had a subtrochanteric pathological fracture after a prolonged intake of alendronate followed by ibandronate.

Les bisphosphonates ont fréquemment démontré leur efficacité dans le traitement de l'ostéoporose, notamment l'ibandronate et l'alendronate. Mais, de plus en plus, il est fait mention dans la littérature de cas de patients traités par un bisphosphonate au long cours et présentant une fracture atypique qui y serait liée. Il s'agit, le plus souvent, de fractures fémorales dans la partie proximale de la diaphyse. Nous rapportons ici le cas d'une patiente de 73 ans ayant subi une fracture pathologique sous-trochantérienne après une prise prolongée d'alendronate suivie d'une prise d'ibandronate.

Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials.

AIM: To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: Data were pooled from 13 placebo-controlled trials of up to 24 weeks' duration (dapagliflozin, n = 2360; placebo, n = 2295). Larger placebo-/comparator-controlled pools of 21 (≤208 weeks; dapagliflozin, n = 5936; control, n = 3403) and 30 trials (≥12 weeks; dapagliflozin, n = 9195; control, n = 4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower limb amputation, respectively. RESULTS: Over 24 weeks, the overall incidence of AEs and serious AEs (SAEs) was similar for dapagliflozin and placebo: 60.0% vs 55.7% and 5.1% vs 5.4%, respectively. Rates of hypoglycaemia, volume depletion AEs, urinary tract infections (UTIs) and fractures were balanced between the groups. Genital infections were more frequent with dapagliflozin (5.5%) vs placebo (0.6%) and renal function AEs occurred in 3.2% vs 1.8% of patients (the most common renal AE was decreased creatinine clearance: 1.1% vs 0.7%). In the 21-study pool, 1 SAE of DKA and 3 AEs of ketonuria/metabolic acidosis occurred with dapagliflozin vs none with control; estimated combined incidence for these events was 0.03% (95% confidence interval 0.010-0.089). In the 30-study pool, lower limb amputation occurred in 8 (0.1%) and 7 (0.2%) patients receiving dapagliflozin and control, respectively. CONCLUSION: The overall incidence rates of AEs and SAEs were similar in the dapagliflozin and placebo/control groups, including the incidence of hypoglycaemia, volume depletion, fractures, UTIs, amputations and DKA. Genital infections were more frequent with dapagliflozin than placebo.

Teriparatide for treatment of patients with bisphosphonate-associated atypical fracture of the femur.

The Fracture Improvement with Teriparatide (Fix-IT) study randomized 13 women with an atypical femur fracture to immediate vs delayed teriparatide therapy; all were followed for 12 months. Results suggested a trend for superior healing and lesser bone mineral density declines in the immediate vs delayed group with no differences in adverse events. PURPOSE: Little clinical data are available on the use of teriparatide for the treatment of bisphosphonate-associated atypical femur fractures (AFF). The goal of the Fix-IT study was to determine if immediate therapy with teriparatide was superior for fracture healing after an AFF compared to a 6-month delay in teriparatide therapy. METHODS: This randomized pilot clinical trial included 13 women with an AFF who were randomized to immediate teriparatide vs a delay of 6 months. All were followed for 12 months on teriparatide. The primary outcomes included individual and composite measures of radiologic bone healing (scored 1 point [no healing] to 4 points [complete healing]) at 6 and 12 months. Secondary outcomes included bone mineral density of the unfractured contralateral hip, spine, 1/3 distal radius, and adverse events. RESULTS: We found there was a trend for superior healing with the composite score (12.6 vs 11.2 at 6 months and 15.4 vs 13.2 at 12 months), and lesser bone mineral density declines at the 1/3 distal radius (12-month change - 1.9 vs - 6.1%) in the immediate vs the delayed group. There were no differences in adverse events. There was one implant failure in the delayed group. CONCLUSIONS: There is a preliminary signal for greater improvements with immediate teriparatide therapy vs delayed therapy. However, because an AFF is a rare event, and only a small number of patients were included, the results must be interpreted with caution.

Teriparatide treatment in an adult patient with hypophosphatasia exposed to bisphosphonate and revealed by bilateral atypical fractures.

Atypical femoral fractures are defined as atraumatic fractures located in the subtrochanteric region or femoral shaft. They have been mainly reported in patients taking bisphosphonates. We report the case of a 67-year-old female with osteoporosis treated by alendronate during ten years. Radiographies showed atypical femoral fractures. Serum levels of total and bone-specific alkaline phosphatase were low. In order to accelerate bone healing, teriparatide was introduced. After one year of teriparatide treatment, pain and functional difficulty have decreased, and alkaline phosphatase levels were normalized. In view of this history of recurrent fractures, of atypical femoral fractures, of early spontaneous loss of teeth, and of low serum total and bone-specific alkaline phosphatase levels, the diagnosis of hypophosphatasia has been considered and confirmed by genetic research. Other conditions than exposure to anti-resorptive therapies may promote atypical femoral fractures, such as in conditions associated with abnormal bone structures, as hypophosphatasia, a rare inherited bone metabolism disorder. A few case reports have reported adult hypophosphatasia treated by teriparatide with a good efficacy on bone pain and consolidation but with mixed results on biological markers. Teriparatide may be therefore a treatment option in adult hypophosphatasia. ALP levels should be carefully checked among osteoporotic patients and specially before introducing a bone resorption inhibitor. Low alkaline phosphatase levels have to be taken into account and an evocative history of hypophosphatasia has to be sought because this condition may expose patients to develop atypical femoral fractures during bisphosphonate treatment.

Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma.

Importance: Daily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health. Objective: To determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma. Design, Setting, and Participants: In this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use. Exposures: Inhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use. Main Outcomes and Measures: First emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Results: This study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (OR, 0.96; 95% CI, 0.86-1.07), or past use (OR, 1.00; 95% CI, 0.91-1.11) of inhaled corticosteroids, compared with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33). Conclusions and Relevance: Systemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.

Management of atypical femoral fracture in a patient with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a generalised connective tissue disorder associated with low bone mass, bone fragility and increased susceptibility to fractures. First-line treatment to improve bone mineral density (BMD) is usually with bisphosphonates but long-term usage has been associated with uncommon complications such as atypical femoral fractures (AFF). Treatment with teriparatide in this situation has been reported with positive outcomes. However, choice of treatment after 2 years of teriparatide has not been well studied or reported. We describe a patient with OI treated with bisphosphonates for 9 years, who then suffered a spontaneous AFF, was subsequently started on teriparatide for 2 years followed by 6 monthly Denosumab. 1 year post-treatment with Denosumab, there was significant improvement in BMD, good fracture healing and no new fractures. This case highlights the potential use of denosumab following 2 years of teriparatide treatment in patients with OI with AFF.