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Purpose of reviewThis review describes the rational for bisphosphonate holidays, summaries key evidence to support the concept, and provides a roadmap to help clinicians initiate, monitor, and discontinue a bisphosphonate drug holiday.Recent findingsRandomized trials and data from large observational studies are available to determine the short and long-term bisphosphonate benefits (prevention of fracture) and harms (principally atypical femoral fractures and osteonecrosis of the jaw). Mounting evidence points towards a causal relationship between bisphosphonate use and AFF and ONJ, particularly with > 5 years of use. Multiple studies now confirm the risk of AFF falls rapidly after BPs are discontinued. Osteoporosis patients without previous hip, vertebral, or multiple non-spine fractures who are successfully treated with oral bisphosphonates for 5 years (3 years if intravenous), should be offered a 3-5 year drug holiday, particularly if hip BMD T-score is > - 2.5. Bisphosphonates should only be continued beyond 10 years (6 years if parenteral) in patients at very high risk of fracture.

Context Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). Objective 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. Methods 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. Results 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Rationale Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk. Methods This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50 years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively. Results The study included 793 815 men (age: 64 ± 10) and 873 524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14 years (IQR: 6.5, 14), 95 372 men and 212 498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices. Conclusions Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices. [ABSTRACT FROM AUTHOR]

Context Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD/MAS, absence of registries, heterogeneous presentation, and possibly asymptomatic phenotype. FD/MAS may present with FGF23-mediated hypophosphatemia, of which the epidemiology is also unclear. Objective Evaluate incidence and prevalence of FD/MAS and FD/MAS-related hypophosphatemia. Methods This cohort study based on the nationwide Danish National Patient Registry from 1995-2018, included patients identified by ICD-10 codes M85.0 (monostotic FD [MFD]) and Q78.1 (polyostotic FD [PFD]/MAS). Incidence rates and prevalence were calculated and stratified by sex, age, calendar period, and diagnosis code. Cases were screened for FD-associated hypophosphatemia by diagnosis code E.83 (disorder of mineral metabolism) and dispatched vitamin D analogues. Results A total of 408 patients were identified, 269 with MFD (66%), 139 with PFD/MAS (34%), comparable between sexes. Incidence of FD/MAS demonstrated increasing secular trend with a rate of 3.6 per 1 000 000 person-years (95% CI: 2.9, 4.5) in 2015-2018. Incidence peaked between age 11 and 20. Prevalence of FD/MAS increased over time to 61.0 (95% CI: 54.6, 67.4) per 1 000 000 persons in 2018. The incidence rate of MFD was 1.5-fold that of PFD/MAS in the first decade, rising to 2.5-fold in the last decade. No FD/MAS cases were registered with diagnosis code or treatment for hypophosphatemia. Conclusion FD/MAS is rare, diagnosis peaks during adolescence without sex predominance, and MFD is most prevalent. Hypophosphatemia may be underdiagnosed and undertreated, or it may be underregistered, comparing this study to literature. [ABSTRACT FROM AUTHOR]