Hydraulic Fracturing Design Optimization Guidelines for Heterogeneous Reservoir

This paper describes the journey of hydraulic fracturing design solutions and implementation in Khazzan field. More than 100 wells have been stimulated with hydraulic fracturing in the field in the last decade. Most of these wells were treated with a single-stage massive propped hydraulic fracturing treatment aimed at stimulating the entire vertical productive zone in a single treatment. More recently, hydraulic fracturing has begun on the southern acreage from Khazzan, referred to as Ghazeer. Producing layers in this area are thicker and higher permeability and, as a result, more prolific. Based on the available data and experiences, the establishment of clear guidelines has become a requirement to help the understanding and adjust the hydraulic fracturing design for each well to be become a well-specific optimum design. During the stimulation journey, surveillance techniques have been utilized and implemented in the Khazzan and Ghazeer fields to provide and develop better understanding of the fracture propagation process. These data have proven essential to support stimulation design evolvement and determine if multiple fracturing stages are justified or whether a single stage would be sufficient. Based on a wide range of hydraulic fracture stimulation operations performed across the Khazzan and Ghazeer fields, a flowchart was developed to integrate all the lessons learned from the previous experience and help optimize future fracture design. Clear guidelines include the rationale between the selection of single or multiple fracturing stages, the selection of optimal pad fractions, and other associated details of the fracture design. This flowchart has been extensively validated with surveillance and has proven its inherent value in many stimulated wells, with either single or multiple proppant fracturing stages.

The influence of snuff and smoking on bone accretion in late adolescence. The Tromsø study, Fit Futures

Summary Areal bone mineral density (aBMD) predicts future fracture risk. This study explores associations between use of tobacco and bone accretion in Norwegian adolescents. Our results indicate that use of snuff is negatively associated with accretion of aBMD in adolescence and may be a signal of increased future fracture risk. Purpose Bone mineral accrual in childhood and adolescence is a long-term primary preventive strategy of osteoporosis. Areal bone mineral density (aBMD) is a surrogate measure of bone strength and a predictor of fracture risk. The aim of this population-based 2-year follow-up cohort study was to explore associations between use of snuff and smoking and changes (∆) in aBMD in Norwegian girls and boys aged 15–17 years at baseline. Methods The first wave of the Tromsø study, Fit Futures was conducted from 2010 to 2011. Femoral neck (FN), total hip (TH), and total body (TB) bone mineral content (BMC) and aBMD were measured by dual-energy X-ray absorptiometry. Information on use of snuff, smoking habits, and other lifestyle related variables were collected through self-administered questionnaires. Two years later, during 2012–2013, the measurements were repeated in the second wave. The present study included 349 girls and 281 boys and compared “non-users” (n = 243 girls, 184 boys) with “users” (n = 105 girls, 96 boys) of snuff and “non-smokers” (n = 327 girls, 249 boys) with “smokers” (n = 21 girls, 31 boys) using linear regression adjusted for age, baseline height and weight, change in height and weight, pubertal maturation, physical activity, ethnicity, alcohol consumption, diagnosis known to affect bone, and medication known to affect bone. The influence of “double use” on bone accretion was also explored. Results In girls, no associations between use of snuff and ∆aBMD were found. In boys, use of snuff was associated with reduced bone accretion in all ∆aBMD models. Sensitivity analysis with exclusion of “sometimes” users of snuff strengthened associations at femoral sites in girls and attenuated all associations in boys. In girls, no associations between smoking and ∆aBMD were found. In boys, only the association with TB ∆aBMD was significant in the fully adjusted models. In girls, “double users” analyses showed similar association to smoking. In boys, nearly all models showed statistically significant associations with a difference of ~ 1–2% in ∆aBMD between “non-users” and “double users” during 2 years of follow-up. Conclusions Our results indicate that tobacco use in late adolescence could be detrimental to bone accretion and may be a signal of increased fracture risk in adult life.

Effects of once-yearly zoledronic acid on bone density and incident vertebral fractures in nonmetastatic castration-sensitive prostate cancer patients with osteoporosis

Background Androgen deprivation therapy (ADT) is the effective treating prostate cancer but is often accompanied by cancer treatment-induced bone loss (CTIBL), which impairs the patient’s quality of life. In patients with nonmetastatic castration-sensitive prostate cancer (M0CSPC) who already have osteoporosis before starting ADT, appropriate bone-modifying agent intervention must be performed in parallel, as the patient has a high risk of future fracture. However, little is known about therapeutic interventions aimed at preventing the progression of CTIBL and new fractures. The present study explored the effect of once-yearly zoledronic acid 5 mg (ZOL 5 mg) on bone mineral density (BMD) and new vertebral fractures (VFs) in M0CSPC patients with coexisting osteoporosis before starting ADT. Methods We conducted a retrospective, multi-institutional, cohort study involving 42 M0CSPC patients with osteoporosis who had undergone ADT with/without a single intravenous infusion of ZOL 5 mg at the start of ADT (ZOL 5 mg group, n = 26; control group, n = 16). The association of the ZOL 5 mg with changes in the BMD from baseline to 12 months and the incidence of VFs were evaluated. Results Prevalent VFs were found in 47.6% of all patients at baseline. ZOL 5 mg significantly increased the lumbar spine BMD (LS-BMD) (mean rate of change: + 4.02%, p < 0.0001) and significantly decreased the TRACP-5b (mean rate of change: − 52.1%, p < 0.0001) at 12 months after starting ADT. Incident VFs were identified in 19.0% of all patients at 12 months after starting ADT. After adjusting for the age, BMI, and changes in the LS-BMD, ZOL 5 mg was not significantly associated with incident VFs (odds ratio 0.66, 95% confidence interval 0.04–11.3, p = 0.7774). Conclusion ZOL 5 mg significantly increased the LS-BMD 12 months after starting ADT, and our short-term results showed that ZOL 5 mg was not significantly correlated with the suppression of incident vertebral fractures.

Osteoporosis: Diagnosis and Management

Abstrak: Osteoporosis merupakan penyakit tulang yang paling sering dijumpai dan memiliki hubungan erat dengan risiko fraktur sehingga merupakan salah satu masalah kesehatan masyarakat yang besar. Penyakit ini lebih sering ditemukan pada perempuan usia lanjut dan dipengaruhi oleh berbagai faktor. Tulisan ini merupakan suatu kajian pustaka dengan tujuan untuk menyampaikan konsep dasar dan pemahaman yang lebih baik yang dibutuhkan dalam pengelolaan penyakit ini. Hasil kajian menunjukkan bahwa pengelolaan penyakit ini membutuhkan strategi tatalaksana yang harus disesuaikan pada setiap pasien, yang meliputi modifikasi gaya hidup, pengelolaan faktor risiko dan terapi farmakologis agar dapat menurunkan morbiditas dan mortalitas serta komplikasi yang ditimbulkan oleh penyakit ini. Dibutuhkan penelitian lanjut untuk memberikan bukti dan memberikan pedoman agar pengelolaan penyakit dapat menjadi lebih baik.Kata kunci: osteoporosis, risiko fraktur, densitas mineral tulang Abstract: Osteoporosis is the most commonly bone disease and is highly associated with an increased risk of future fracture furthermore makes it a major public health problem. The disease is most prevalent in older females with multifactorial etiology. This was a literature review using relevant articles. The aim of this study was to provide basic concept and better understanding which is needed to manage the disease. This review showed that individualized treatment strategy is needed. Lifestyle modification, risk factor management, and pharmacological treatment are required to deal with the condition as well as reduced morbidity and mortality caused by the disease and its complication. Further study of this disease needs to be conducted to provide more evidences and guidelines to achieve better management of the disease.Keywords: osteoporosis, fracture risk, bone mineral density

Bone age is not just for kids

More informed discussions between physicians and older adults about the consequences of an initial osteoporotic fracture could encourage more patients to consider treatments that protect against future fracture.

The International Collaborative Gaucher Group GRAF (Gaucher Risk Assessment for Fracture) score: a composite risk score for assessing adult fracture risk in imiglucerase-treated Gaucher disease type 1 patients

Background Fractures in Gaucher disease type 1 (GD1) patients cause significant morbidity. Fracture risk may be decreased by enzyme replacement therapy (ERT) but not eliminated. When considering initiation of treatment, it is useful to know to what extent fixed patient-specific factors determine risk for future fractures beyond standard risk factors that change with time and treatment, such as decreased bone mineral density. We developed a tool called the GRAF score (Gaucher Risk Assessment for Fracture) that applies 5 widely available characteristics (sex, age at treatment initiation [ATI], time interval between diagnosis and treatment initiation, splenectomy status, history of pre-treatment bone crisis) and provides a practical method to assess future fracture risk when imiglucerase ERT is initiated. Methods Inclusion criteria: GD1 patients in the International Collaborative Gaucher Group Gaucher Registry as of September 2019 initially treated with alglucerase/imiglucerase; known splenectomy status; at least one skeletal assessment on treatment (3216 of 6422 patients). Data were analyzed by ATI group (< 18, ≥ 18 to < 50, or ≥ 50 years of age) using Cox proportional hazards regression with all 5 risk factors included in the multivariable model. A composite risk score was calculated by summing the contribution of each parameter weighted by the strength of its association (regression coefficient) with fracture risk. Results Patients were followed from the date of treatment initiation (or age 18 years for patients if treatment started earlier) to the date of first adult fracture (n = 288 first fracture endpoints), death, or end of follow-up. The GRAF score for each ATI group was associated with a 2.7-fold increased risk of adult fracture for each one-point increase (p < 0.02 for < 18 ATI, p < 0.0001 for ≥ 18 to < 50 ATI and ≥ 50 ATI). Conclusions The GRAF score is a tool to be used with bone density and other modifiable, non-GD-specific risk factors (e.g. smoking, alcohol intake, frailty) to inform physicians and previously untreated GD1 patients about risk for a future fracture after starting imiglucerase regardless of whether there is an eventual switch to an alternative ERT or to substrate reduction therapy. GRAF can also help predict the extent that fracture risk increases if initiation of treatment is further delayed.

The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures

A functional polymorphism in methylenetetrahydrofolatereductase (MTHFR) has been identifi ed at codon677 (C677T). The T-allele variant (valine type) has lowerenzyme activity than the wild type (C-allele or alaninetype), resulting in a slightly elevated homocysteine level,which has been recently recognized as a risk factor for fracture.However, whether subjects bearing the T allele havehigher susceptibility to fractures is still controversial. Wehave investigated the effects of MTHFR polymorphism onfracture susceptibility in Japanese postmenopausal women.A total of 502 postmenopausal ambulatory Japanese womenwere followed up for 5.1 ± 3.4 (mean ± SD) years, and atotal of 155 patients with incident fractures (121 patientswith vertebral fractures and 34 cases with fractures at othersites) were recorded. When compared with the patientswithout any fractures, the patients with incident fractureswere older, had more prevalent fractures, had higher urinarylevels of bone turnover markers as well as plasma homocysteinelevel, but were shorter in body height and had lowerbone mineral density. The prevalence of the TT genotypeof MTHFR was signifi cantly higher in the patients withincident fractures compared to the other genotypes. Thesubjects with the TT genotype had a higher incidence rateof fracture and higher plasma level of homocysteine thanthe subjects bearing the non-TT genotype. This relationshipwas observed in both osteoporotic and nonosteoporoticgroups. The hazard ratio for TT genotype without osteoporosis,non-TT genotype with osteoporosis, and TT genotypewith osteoporosis was 1.49 (0.91–2.45), 3.64 (2.50–5.29),and 7.21 (4.34–11.97), respectively, compared to the non-TTgenotype without osteoporosis. A higher hazard ratio forthe TT genotype with osteoporosis was still apparent afteradjustment for age, body size, and number of prevalentvertebral fractures. These results indicate that the TT genotypeof MTHFR may be a risk factor for future fracture inaddition to the traditional risk factors.

Prediction of a new fracture after a wrist fracture – a five year follow up

Background Falls and ensuing fractures are major challenges in our ageing population. The aim of this study was to study if clinical balance measures, function of the inner ear, self-rated health or fracture risk assessed by FRAX ® could predict future admission to hospital because of a fracture among a group of older persons with previous wrist fracture. Methods This was a longitudinal study with a 5-year follow-up. Searches in the local health authority’s patient administrative system (PAS) were performed 5 years after inclusion and baseline measurements were taken. Information was extracted about whether participants had been treated for a fracture or hospitalized other reasons during the 5-year period. Persons, 50 years and above, with previous wrist fracture (n=83). Five different clinical balance measures was assessed, postural sway was assessed by means of a force plate, vestibular asymmetry was assessed with the head- shake test, self-rated health by EuroQol 5 Dimension visual analogue scale and risk of future fracture by the Fracture Risk Assessment Tool (FRAX ® ). Age and body mass index was also used in the risk analysis. Results Age was associated with risk of future fracture, OR 1,06 (95% CI 1,01-1,12). The ability to stand on one leg with eyes open correlated significantly with future fracture (p=0.011) and so did FRAXosteo, however on the limits of significance (p=0.052). Conclusion This follow-up study showed that the one-leg standing time-test was a stronger predictor for future facture within five-years after a wrist fracture than FRAX not including a measure of balance.