Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

Treatment indications and thresholds of intervention: consensus and controversies in osteoporosis.

A few indications for treatment and thresholds for intervention in osteoporosis have been propounded in the literature and recommended in guidelines. These include a bone mineral density (BMD) T-score ≤ -2.5, fracture probability-based scores and the presence of a fragility fracture. A low BMD is associated with an increased risk of fracture. However, a BMD T-score of ≤ -2.5 on its own does not capture fracture risk in its entirety. Fracture risk assessment tools that are based on clinical risk factors arose from the misgivings about using BMD T-scores in isolation to assess fracture risk. Algorithms such as FRAX, Garvan etc, integrate various clinical risk factors with or without BMD to compute the probability of a hip fracture or a major osteoporotic fracture over a finite period. These probabilities do not yield distinctive thresholds by themselves and need to be interpreted wisely and adopted by consensus. Evidence exists to show that treatment can decrease the risk of sustaining a second fracture. Therefore, patients with a fragility fracture should be considered for treatment. In this narrative interview, we will explore the strengths and limitations of some of these indications for treatment and will discuss the various points of contention surrounding them.

Evaluating the long-term impact of projected climate on rice-lentil-groundnut cropping system in Lower Gangetic Plain of India using crop simulation modelling.

Most simulations of food production in response to various climates to date have used simulations of the same crop over multiple years. This study evaluated the impact of projected climate on performance of rice-lentil-groundnut cropping sequence in New Alluvial Zone of West Bengal, India, using DSSAT model. The study period consisted of baseline (1980-2010), mid-century (2040-2069) and end-century (2070-2099). Advancement in days to anthesis (2-13 days) was simulated for rice during the future periods. For lentil and groundnut, average advancement in days to anthesis was 1 day. Days to maturity were shortened by 3-16 days for rice and 0-7 days for lentil. Nevertheless, for groundnut, the days to maturity were simulated to increase by 1-9 days. The impact on final biomass and yield was simulated with and without CO2 fertilization, and the positive impact of CO2 fertilization was prominent for all the three crops. When CO2 fertilization effect was considered, the yield of rice was projected to increase by 11-32%. On the other hand, yield of lentil and groundnut was estimated to change by - 31 to - 12% and - 33 to + 8%, respectively. Enhanced CO2 could mitigate the magnitude of yield reduction due to enhanced temperature. Rice was benefited due to the carryover effect of residue from preceding groundnut and, hence, could sustain the yield on a long term. The study could also quantify the uncertainty in simulation of yield due to selection of GCMs.

Cost-effectiveness of FRAX®-based intervention thresholds for management of osteoporosis in Singaporean women.

Cost-effectiveness analysis of FRAX® intervention thresholds (ITs) in Singaporean women > 50 years of age showed that generic alendronate was cost-effective at age-dependent major osteoporotic fracture (MOF) IT from the ages of 65 years for both full and real-world adherence whilst hip fracture (HF) ITs were cost-effective from the ages of 60 and 65 years. Alendronate was cost-effective irrespective of age only at fixed MOF IT of 14% and HF IT of 3.5%. INTRODUCTION: FRAX®-based intervention thresholds (ITs) were recently identified for osteoporosis management in Singapore. This study aimed to assess the cost-effectiveness of ITs in Singaporean women over the age of 50 years. METHODS: A validated Markov microsimulation model was used to estimate the lifetime healthcare costs (SGD2019) per quality-adjusted life-years (QALY) of generic alendronate compared with no treatment. Cost-effectiveness of age-dependent FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) ITs was explored. In addition, ITs that would lead to cost-effectiveness were computed. Fracture incidence and cost data were obtained from the Ministry of Health and a previously published Singaporean study. A cost-effectiveness threshold of SGD 62,500/QALY gained was used, based conservatively on 0.7 times the Singapore GDP per capita. RESULTS: Generic alendronate was shown to be cost-effective at MOF ITs from the ages of 65 years, while HF ITs were cost-effective from the ages of 60 and 65 years, assuming full and real-world adherence, respectively. A 14% MOF and a 3.5% HF ITs were required for alendronate to be cost-effective above 50 years. CONCLUSION: This study suggests that the treatment of Singaporean women with alendronate is cost-effective at age-dependant FRAX® intervention thresholds at 65 years and older. Furthermore, identifying women at any age above 50 years with a 10-year risk of MOF or HF of 14% or 3.5% would lead to efficient use of resources. Cost-effective access to therapy for patients at high fracture probability based on FRAX® could contribute to reduce the growing burden of osteoporotic fractures in Singapore.

Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services.

Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

IQ driving QI: the Asia Pacific Consortium on Osteoporosis (APCO): an innovative and collaborative initiative to improve osteoporosis care in the Asia Pacific.

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region. INTRODUCTION: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region. METHODS: APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis. RESULTS AND CONCLUSIONS: The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.

Correction to: Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures.

The article 'Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures',written by J. A. Kanis, was originally published Online First without Open Access. After publication in volume [#], issue [#] and page [#-#], the author decided to opt for Open Choice and to make the article an Open Access publication.

Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures.

Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. INTRODUCTION: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. METHODS: Clinical perspective and updated literature search. RESULTS: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. CONCLUSIONS: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.

Recommendations for the conduct of economic evaluations in osteoporosis: outcomes of an experts' consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the US branch of the International Osteoporosis Foundation.

Economic evaluations are increasingly used to assess the value of health interventions, but variable quality and heterogeneity limit the use of these evaluations by decision-makers. These recommendations provide guidance for the design, conduct, and reporting of economic evaluations in osteoporosis to improve their transparency, comparability, and methodologic standards. INTRODUCTION: This paper aims to provide recommendations for the conduct of economic evaluations in osteoporosis in order to improve their transparency, comparability, and methodologic standards. METHODS: A working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis to make recommendations for the design, conduct, and reporting of economic evaluations in osteoporosis, to define an osteoporosis-specific reference case to serve a minimum standard for all economic analyses in osteoporosis, to discuss methodologic challenges and initiate a call for research. A literature review, a face-to-face meeting in New York City (including 11 experts), and a review/approval by a larger group of experts worldwide (including 23 experts in total) were conducted. RESULTS: Recommendations on the type of economic evaluation, methods for economic evaluation, modeling aspects, base-case analysis and population, excess mortality, fracture costs and disutility, treatment characteristics, and model validation were provided. Recommendations for reporting economic evaluations in osteoporosis were also made and an osteoporosis-specific checklist was designed that includes items to report when performing an economic evaluation in osteoporosis. Further, 12 minimum criteria for economic evaluations in osteoporosis were identified and 12 methodologic challenges and need for further research were discussed. CONCLUSION: While the working group acknowledges challenges and the need for further research, these recommendations are intended to supplement general and national guidelines for economic evaluations, improve transparency, quality, and comparability of economic evaluations in osteoporosis, and maintain methodologic standards to increase their use by decision-makers.

Diagnosis and management of bone fragility in diabetes: an emerging challenge.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.

Quantification of annual sediment deposits for sustainable sand management in Aghanashini river estuary.

Sedimentation involving the process of silt transport also carries nutrients from upstream to downstream of a river/stream. Sand being one of the important fraction of these sediments is extracted in order to cater infrastructural/housing needs in the region. This communication is based on field research in the Aghanshini river basin, west coast of India. Silt yield in the river basin and the sedimentation rate assessed using empirical techniques supplemented with field quantifications using soundings (SONAR), show the sediment yield of 1105-1367 kilo cum per year and deposition of sediment of 61 (2016) to 71 (2015) cm. Quantifications of extractions at five locations, reveal of over exploitation of sand to an extent of 30% with damages to the breeding ground of fishes, reduced productivity of bivalves, etc., which has affected dependent people's livelihood. This study provides vital insights towards sustainable sand harvesting through stringent management practices.

Indian summer heat wave of 2015: a biometeorological analysis using half hourly automatic weather station data with special reference to Andhra Pradesh.

Heat wave is a hazardous weather-related extreme event that affects living beings. The 2015 summer heat wave affected many regions in India and caused the death of 2248 people across the country. An attempt has been made to quantify the intensity and duration of heat wave that resulted in high mortality across the country. Half hourly Physiologically Equivalent Temperature (PET), based on a complete heat budget of human body, was estimated using automatic weather station (AWS) data of four locations in Andhra Pradesh state, where the maximum number of deaths was reported. The heat wave characterization using PET revealed that extreme heat load conditions (PET >41) existed in all the four locations throughout May during 2012-2015, with varying intensity. The intensity and duration of heat waves characterized by "area under the curve" method showed good results for Srikakulam and Undi locations. Variations in PET during each half an hour were estimated. Such studies will help in fixing thresholds for defining heat waves, designing early warning systems, etc.

Total and methyl mercury in the water, sediment, and fishes of Vembanad, a tropical backwater system in India.

Mercury contamination in the water bodies of developing countries is a serious concern due to its toxicity, persistence, and bioaccumulation. Vembanad, a tropical backwater lake situated at the southwest coast of India, is the largest Ramsar site in southern India. The lake supports thousands of people directly and indirectly through its resources and ecosystem services. It is highly polluted with toxic pollutants such as heavy metals, as it receives effluent discharges from Kerala's major industrial zone. In the present study, water, pore water, sediment, and fish samples collected from Vembanad Lake were analysed for total mercury (THg) and methyl mercury (MHg) contents. The maximum concentrations of THg and MHg in surface water samples were31.8 and 0.21 ng/L, respectively, and those in bottom water samples were 206 and 1.22 ng/L, respectively. Maximum concentration of THg in surface sediment was observed during monsoon season (2850 ng/g) followed by that in the pre-monsoon season (2730 ng/g) and the post-monsoon season (2140 ng/g). The highest sediment concentration of MHg (202.02 ng/g) was obtained during monsoon season. The spatial variation in the mercury contamination clearly indicates that the industrial discharge into the Periyar River is a major reason for pollution in the lake. The mercury pollution was found to be much higher in Vembanad Lake than in other wetlands in India. The bioaccumulation was high in carnivorous fishes, followed by benthic carnivores. The THg limit in fish for human consumption (0.5 mg/kg dry wt.) was exceeded for all fish species, except for Glossogobius guiris and Synaptura orientalis. The concentration of THg was five times higher in Megalops cyprinoides and four times higher in Gazza minuta. Significant variation was observed among species with different habits and habitats. Overall, risk assessment factors showed that the mercury levels in the edible fishes of Vembanad Lake can pose serious health impacts to the human population.

Probabilistic assessment of phenophase-wise agricultural drought risk under different sowing windows: a case study with rainfed soybean.

A new methodology for crop-growth stage-specific assessment of agricultural drought risk under a variable sowing window is proposed for the soybean crop. It encompasses three drought indices, which include Crop-Specific Drought Index (CSDI), Vegetation Condition Index (VCI), and Standardized Precipitation Evapotranspiration Index (SPEI). The unique features of crop-growth stage-specific nature and spatial and multi-scalar coverage provide a comprehensive assessment of agricultural drought risk. This study was conducted in 10 major soybean-growing districts of Madhya Pradesh state of India. These areas contribute about 60% of the total soybean production for the country. The phenophase most vulnerable to agricultural drought was identified (germination and flowering in our case) for each district across four sowing windows. The agricultural drought risk was quantified at various severity levels (moderate, severe, and very severe) for each growth stage and sowing window. Validation of the proposed new methodology also yielded results with a high correlation coefficient between percent probability of agricultural drought risk and yield risk (r = 0.92). Assessment by proximity matrix yielded a similar statistic. Expectations for the proposed methodology are better mitigation-oriented management and improved crop contingency plans for planners and decision makers.

Dissipation kinetics and effect of processing on imidacloprid and its metabolites in cardamom (Elettaria cardamomum Maton).

Dissipation behaviour of the chloronicotinyl insecticide, imidacloprid (Tatamida 17.8 % SL), in fresh and cured cardamom capsules was studied following application at doses 20 and 40 g a.i. ha(-1) in a cardamom plantation of Indian Cardamom Hills (ICH), Idukki, Kerala, India. A single-laboratory ultra performance liquid chromatography mass spectrometry (UPLC-MS/MS) method was developed and validated for the estimation of imidacloprid and its six metabolites (5-hydroxy, olefin, guanidine, urea, 6-chloronicotinic acid and nitrosimine) in fresh and cured cardamom. At the lower dose, the initial deposits of total imidacloprid residues were 1.91 and 7.23 µg g(-1), respectively, in fresh and cured cardamom. At the higher dose, the initial residues were 3.94 and 14.72 µg g(-1), respectively, in fresh and cured capsules. The residues dissipated below the quantitation level of 0.01 µg g(-1) after 21 and 28 days at lower dose and after 28 days for both at higher dose. The half-lives of imidacloprid in fresh and cured cardamom were 4.02 and 3.63 days, respectively, at lower dose and 3.61 days for both at higher dose. The waiting periods of imidacloprid on fresh and cured cardamom at lower and higher doses were 21.40, 27.10, 23.85 and 30.70 days, respectively. The mean processing factor of imidacloprid was 3.96 at 20 g a.i. ha(-1). Amongst metabolites of imidacloprid, urea had maximum residues in fresh and cured cardamom followed by 5-hydroxy and guanidine. Other metabolites such as 6-chloronicotinic acid, olefin and nitrosimine were not detected either in fresh or cured cardamom.

Mercury in the sediments of Vembanad Lake, western coast of India.

Mercury, a global pollutant, is popping up in places where it was never expected before and it burdens in sediments and other non-biological materials. It is estimated to have increased up to five times the pre-human level due to anthropogenic activities. Vembanad backwaters, one of the largest Ramsar site in India, which have extraordinary importance for its hydrological function, are now considered as one of the mercury hot spots in India. In this study, surface sediment samples of Vembanad Lake and nearshore areas have been seasonally analysed for total mercury and methyl mercury concentrations while the core sediment samples were analysed for total mercury. The results showed that the northern part of the lake was more contaminated with mercury than the southern part. The mercury concentration was relatively high in the subsurface sediment samples, indicating the possibility of historic industrial mercury deposition. A decreasing trend in the mercury level towards the surface in the core sediment was also observed. The geochemical parameters were also analysed to understand the sediment mercury chemistry. Anoxic conditions, pH and organic carbon, sulphur and Fe determined the presence of various species of mercury in the sediments of Vembanad Lake. The prevailing physical and geochemical conditions in Vembanad Lake have indicated the chances of chemical transformation of mercury and the potential hazard if the deposited mercury fractions are remobilised.

Persistence and effect of processing on reduction of fipronil and its metabolites in chilli pepper (Capsicum annum L.) fruits.

A single laboratory UPLC-MS/MS method was developed and validated for the estimation of fipronil and its metabolites in fresh and dry chilli pepper fruits. Dissipation of fipronil on chilli fruits was studied following the application of fipronil (Jump 80 WG) at 40 and 80 g active ingredient (a.i.) ha(-1) in the fruiting stage of the crop. The initial deposits of total fipronil on fresh chilli fruits at single and double dose application were 0.69 and 1.43 µg g(-1), respectively, and were dissipated to below quantitation level at 27 days after application. The half-life of fipronil at single and double dose in fresh chilli pepper was 4.22 and 4.32 days and the waiting period was 25.9 and 30.6 days, respectively. Processing factor due to sun drying was calculated by measuring fipronil residues in dry chilli fruits, and it ranged from 2.96 to 3.50 during 0 to 21st day after application. Among the metabolites of fipronil, fipronil desulfenyl and fipronil sulfone had maximum residues in fresh and dried chilli, respectively, followed by fipronil sulfide. Dipping in solutions of tamarind, turmeric, vinegar and slaked lime and wet scrubbing could remove more than 90% of fipronil residues in fruits.