This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE.

After liver and lungs, bone is the third most common metastatic site (Nystrom et al., 1977). Almost all malignancies can metastasize to the skeleton but 80% of bone metastases originate from breast, prostate, lung, kidney and thyroid cancer (Mundy, 2002). Introduction of effective systemic treatment in many cancers has prolonged patients\' survival, including those with bone metastases. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications, such as pain and neurologic compromise. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. In turn, growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment avoiding development of SRE. The treatment for bone metastases should focus on relieving existing symptoms and preventing new ones. Radiotherapy is the standard of care for patients with symptomatic bone metastases, providing durable pain relief with minimal toxicity and reasonable cost-effectiveness. Historically, the dose was prescribed in one to five fractions and delivered using simple planning techniques. While 3D-conformal radiotherapy is still widely used for treating bone metastases, introduction of highlyconformal radiotherapy techniques such as stereotactic body radiotherapy (SBRT) have opened new therapeutic possibilities that should be considered in selected patients with bone metastases.

BACKGROUND: The recently developed fracture-related infection (FRI) consensus definition, which is based on specific diagnostic criteria, has not been fully validated in clinical studies. We aimed to determine the diagnostic performance of the criteria of the FRI consensus definition and evaluated the effect of the combination of certain suggestive and confirmatory criteria on the diagnostic performance.
METHODS: A multicenter, multi-national, retrospective cohort study was performed. Patients were subdivided into an FRI or a control group, according to the treatment they received and the recommendations from a multidisciplinary team (\'intention to treat\'). Exclusion criteria were patients with an FRI diagnosed outside the study period, patients younger than 18 years of age, patients with pathological fractures or patients with fractures of the skull, cervical, thoracic and lumbar spine. Minimum follow up for all patients was 18 months.
RESULTS: Overall, 637 patients underwent revision surgery for suspicion of FRI. Of these, 480 patients were diagnosed with FRI, treated accordingly, and included in the FRI group. The other 157 patients were included in the control group. The presence of at least one confirmatory sign was associated with a sensitivity of 97.5%, a specificity of 100% and a high discriminatory value (AUROC 0.99, p < 0.001). The presence of a clinical confirmatory criterion or, if not present, at least one positive culture was associated with the highest diagnostic performance (sensitivity: 98.6%, specificity: 100%, AUROC: 0.99 (p < 0.001)). In the subgroup of patients without clinical confirmatory signs at presentation, specificities of at least 95% were found for the clinical suggestive signs of fever, wound drainage, local warmth and redness.
CONCLUSIONS: The presence of at least one confirmatory criterion identifies the vast majority of patients with an FRI and was associated with an excellent diagnostic discriminatory value. Therefore, our study validates the confirmatory criteria of the FRI consensus definition. Infection is highly likely in case of the presence of a single positive culture with a virulent pathogen. When certain clinical suggestive signs (e.g., wound drainage) are observed (individually or in combination and even without a confirmatory criterion), it is more likely than not, that an infection is present.

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.
BACKGROUND: 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.

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system.

Single fraction radiation treatment (SFRT) is recommended for its equivalence to multiple-fraction (MF) RT in the palliation of uncomplicated bone metastases (BM). However, adoption of SFRT has been slow.
Literature searches for studies published following 2014 were conducted using online repositories of gray literature, Ovid MEDLINE, Embase and Embase Classic, and the Cochrane Central Register of Controlled Trials databases.
A total of 32 articles detailing patterns of practice and clinical practice guidelines were included for final synthesis. The majority of organizations have released high level recommendations for SFRT use in treatment of uncomplicated BM, based on evidence of non-inferiority to MFRT. There are key differences between guidelines, such as varying strengths of recommendation for SFRT use over MFRT; contraindication in vertebral sites for SFRT; and risk estimation of pathologic fractures after SFRT. Differences in guidelines may be influenced by committee composition and organization mandate. Differences in patterns of practice may be influenced by individual center policies, payment modalities and consideration of patient factors such as age, prognosis, and performance status.
Although there is some variation between groups, the majority of guidelines recommend use of SFRT and others consider it to be a reasonable alternative to MFRT.

BACKGROUND: The cost of fragility fractures to the UK economy is predicted to reach £2.2 billion by 2025. We studied our hip fracture population to establish whether national guidelines on fragility fracture prevention were being followed, and whether high risk patients were identified and treated by local care services.
METHODS: Data on a consecutive series of trauma hip fracture admissions were collected prospectively over 14 months. National Institute for Health and Care Excellence (NICE) and National Osteoporosis Guideline Group (NOGG) recommendations and FRAX(®) risk calculations were applied to patients prior to their admission with a new hip fracture.
RESULTS: Overall, 94 patients were assessed against national guidelines. The mean population age was 77 years. Almost a quarter (22%) of patients had suffered a previous fragility fracture. The mean FRAX(®) ten-year probability of hip fracture was 7%. According to guidelines, 45% of the study population required treatment, 35% fulfilled criteria for investigation and reassessment, and 20% needed no further management. In practice, 27% received treatment, 4% had undergone dual energy x-ray absorptiometry and were untreated, and 69% had not been investigated and were untreated. In patients meeting intervention thresholds, only 33% of those who required treatment were receiving treatment in practice.
CONCLUSIONS: In conjunction with NICE and NOGG recommendations, FRAX(®) was able to identify 80% of our fracture population as intermediate or high risk on the day of fracture. Correct management was evident in a third of cases with a pattern of inferior guideline compliance seen in a London population. There remains a lack of clarity over the duty of care in fragility fracture prevention.

Glucocorticoids (GCs) were widely used for the treatment of various disorders. Since GC-induced bone loss is most rapid during the initial 3 - 6 months and primary prevention of bone loss is especially important, guidelines for management of GC-induced osteoporosis have been published overseas and in Japan. In response to changes in the circumstances surrounding GIO regarding fracture assessment tool and drug therapy, ACR revised recommendations incorporated FRAX®, the WHO fracture risk assessment tool and the Japanese Society of Bone and Mineral Research have finished revision work of the guidelines and the updated guideline will be published soon.

The aim of osteoporosis treatment is to reduce fracture risk. Many kinds of anti-osteoporosis drugs are available in these days, and most of them increase bone mineral density and reduce the risk of fractures. Japanese 2011 guidelines for prevention and treatment of osteoporosis documents the recommendation level of each osteoporosis drugs. It is important to select drugs appropriate for each osteoporosis patient considering the mechanisms of drug action and their clinical efficiency.

The goals of osteoporosis treatment are prevention of fracture. If the patients with higher risk of fragility fractures are treated, the larger effect on reduction of the risk of fragility fractures is expected. Criteria for initiating pharmacological treatment in U.S.A or Europe are based on cost-effectiveness. In Japan, the criteria for initiating pharmacological treatment to prevent fragility fracture were established in the revised version of 2011 guidelines for prevention and treatment of osteoporosis. In these criteria, postmenopausal women and men age 50 and older with vertebral fracture are considered for treatment regardless of bone density. FRAX® was newly introduced to consider whether or not to initiate pharmacological treatment in persons without a fragility fracture who have a low bone mass.