Osteoporosis due to glucocorticoid use in children with chronic illness

Osteoporosis is increasingly recognized as a complication of chronic childhood illnesses, particularly when glucocorticoids (GCs) are necessary for treatment. Elucidation of the mechanisms leading to bone fragility in these settings requires disentanglement of the relative contributions of myriad risk factors, including disease activity, muscle weakness, immobilization, delayed growth and puberty, compromised nutrition, and osteotoxic medications. Over the years, bone mass and density evaluations by dual energy X-ray absorptiometry (DXA) have become popular for assessing bone health in children; however, such measurements are difficult to interpret because of the confounding effect of bone size and the lack of DXA-based densitometric criteria for defining osteoporosis in childhood. Recently, a new diagnostic approach for evaluation of densitometric data in children has been suggested, driven by Frost's mechanostat theory. A diagnostic algorithm based on the mechanostat theory of bone-muscle development is proposed for the characterization of bone disease in children with chronic illness. In addition to DXA-based assessments, techniques such as peripheral quantitative computerized tomography and ilial histomorphometry, for which there are pediatric reference data, are gaining ground in the characterization of skeletal changes due to chronic illness. Although these diagnostic techniques expand our understanding of osteoporosis in children, they do not replace clinical assessment. Concrete clinical evidence for GC-induced bone fragility can be seen in spinal changes due to vertebral compression, with spinal morphometry emerging as an essential, but frequently overlooked, tool in the evaluation of children's bone health. Presently, osteoporosis treatment in the chronic illness setting remains experimental and should be restricted to clinical studies. Following an understanding of the natural history of GC-induced osteoporosis in children, randomized, placebo-controlled prevention and intervention trials will be the next step toward the development of clinical practice guidelines.     

Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study

Background

Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood.

Methods and Findings

The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults'' shorter height and lower self-reported exercise intensity.

Conclusions

Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors'' Summary     

Guías de práctica clínica para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales

ObjectiveTo provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions.ParticipantsMembers of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist.MethodsRecommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND “osteoporosis”, “fractures”, “bone mineral density”, and “treatment”. Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group.ConclusionsThe document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed.     

Osteoporosis in Men

ObjectiveTo review information pertinent to bone health and osteoporosis in men.MethodsA review of pertinent literature was conducted.ResultsOsteoporosis affects approximately 2 million men in the US and accounts for an estimated 600,000 fractures each year. There are significant differences in skeletal size and structure between men and women that account for differences in fracture incidence, location, and outcomes. Bone density testing is appropriate for men age 70 and older and younger men (50-69) who have risk factors for osteoporosis. Lifestyle management, including adequate calcium and vitamin D intake, appropriate physical activity, and avoidance of tobacco and heavy alcohol use, is appropriate for all men. Pharmacologic therapy to reduce fracture risk is advisable for men with a clinical diagnosis of osteoporosis (a spine or hip fracture) or a T-score of −2.5 or below in the spine, femoral neck, total hip or 1/3 radius; however, the majority of men at high risk will only be identified using a fracture risk assessment tool, such as FRAX. Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options.ConclusionOsteoporosis in men presents an important public health problem with significant morbidity and mortality. There are recommended strategies for identifying men at high risk of fracture, and effective agents are available for treatment. (Endocr Pract. 2013;19:834-838)     

Measuring bone mass in children: can we really do it?

Bone densitometry is used to assess skeletal health in clinical and research settings, with the goal of achieving reproducible measurements of bone mass that help to identify individuals predisposed to fracture. The search is now on for better methods of capturing additional factors that contribute to bone strength, including bone size, geometry, microarchitecture, and turnover rates. This has proved particularly challenging in growing children, whose bones continually change in size, shape, and mass. Dual energy X-ray absorptiometry is the preferred method for measuring bone mass in children, but the technique has several limitations, and interpreting the findings can be problematic. Peripheral quantitative computed tomography is a promising method for assessing bone mass and other indices correlating with bone strength, but a lack of precision and paediatric norms currently restricts its clinical utility. Although bone mineral density is predictive of future fracture risk in adults, the evidence in children is less conclusive, and a diagnosis of osteoporosis in a child should not be made on densitometric findings alone. Developing a clearer understanding of how measures of bone mass and strength correlate with bone fracture in children will help target preventive strategies for those in greatest need.     

Adolescents with childhood-onset GHD: how do we get them to peak bone mass?

The development of osteoporosis, with its attendant risk of fragility fracture, is in part related to the peak bone mass (PBM) achieved in early adulthood. Adolescence is a critical time for the acquisition of bone mass, with around 40% of skeletal mass being accrued during pubertal maturation. Growth hormone (GH) plays an integral role in the achievement of PBM after completion of linear growth, and several recent studies have suggested that GH replacement should continue in individuals with childhood-onset GHD until PBM has been attained - irrespective of the height achieved. In those with severe GHD after growth and pubertal development are complete, a seamless transition of GH therapy into adult life may be preferable to allowing a gap in GH treatment. The 'window of opportunity' concept for achieving PBM will, nevertheless, continue to be challenged by GHD teenagers who may resent the seamless continuation of GH replacement beyond adolescence. Preparation for this possibility should therefore begin during childhood, with all GHD teenagers being encouraged to remain on GH therapy until at least their mid-20s.     

血清尿素氮、碱性磷酸酶与儿童营养不良的相关性分析

摘要 目的：探讨血清尿素氮（BUN）、碱性磷酸酶（AKP）与儿童营养不良的相关性。方法：选择2017年10月至2022年10月我院接诊的108例儿童,根据是否存在营养不良将受试儿分为营养不良组（38例）和营养良好组（70例）。检测血清BUN、AKP水平,分析BUN、AKP与受试儿身体组分的相关性。多因素Logistic回归分析影响儿童营养不良的因素,受试者工作特征曲线（ROC）分析BUN、AKP诊断儿童营养不良的价值。结果：营养不良组血清BUN、AKP水平,体脂百分含量（fat percentage,F%）、总体脂肪（TBF）、瘦体重（LBM）低于营养良好组（P＜0.05）。儿童血清BUN、AKP水平与F%、TBF、LBM呈正相关（P＜0.05）。消化不良是儿童营养不良的危险因素（P＜0.05）,出生体质量、BUN、AKP、LBM是儿童营养不良的保护因素（P＜0.05）。联合BUN和AKP诊断儿童营养不良的曲线下面积为0.879,高于单独BUN和AKP诊断（P＜0.05）。结论：营养不良儿童血清BUN、AKP水平降低,且与身体组分改变和营养不良风险增加有关,联合检测血清BUN和AKP水平有助于评估儿童营养不良风险。     

Reference Values of Skeletal Muscle Mass for Korean Children and Adolescents Using Data from the Korean National Health and Nutrition Examination Survey 2009-2011

BackgroundSkeletal muscle mass (SMM) plays a crucial role in systemic glucose metabolism.ObjectiveTo obtain reference data on absolute and relative values of SMM for Korean children and adolescents.MethodsCross-sectional results from 1919 children and adolescents (1024 boys) aged 10–18 years that underwent dual-energy X-ray absorptiometry (DXA) during the Korean National Health and Nutrition Examination Survey 2009–2011 were analyzed. SMMs were evaluated as follows; absolute SMM (appendicular skeletal muscle mass [ASM]) and relative SMMs, namely, height-adjusted skeletal muscle index (SMI; ASM/height²), %SMM (ASM/weight x 100), and skeletal muscle-to-body fat ratio (MFR; ASM/body fat mass).ResultsPercentile curves illustrated the developmental patterns of the SMMs of Korean children and adolescents. ASM and SMI increased with age in both genders, and increased from age 10 throughout adolescence in boys, whereas in girls, they increased until age 13 and then stabilized. In boys, %SMM and MFR were highest at age 15 and then slowly stabilized or decreased, whereas in girls, they peaked at age 10 to 11 and then decreased through adolescence. Cut-off values for low MFR were identified and a significant association was found between a low MFR and high risk of metabolic syndrome. However, this association was found to be dependent on gender and the level of BMI.ConclusionThis study provides reference values of absolute and relative SMM for Korean children and adolescents. Detailed body composition analyses including skeletal muscle and fat mass might provide improved measures of metabolic risk.     

Low bone mass may not be the only cause of skeletal fragility in osteoporosis

Skeletal fragility in postmenopausal osteoporosis is not due solely to reduction in bone mass. This fact explains some of the overlap in bone mineral measurements observed between patients who are fracturing and age- and sex-matched normals who are not. Changes in skeletal architecture and bone remodeling occur with age which can account for some of the fragility. These changes are exaggerated in patients with postmenopausal osteoporosis who are suffering spine fractures. Three abnormalities have been described by histomorphometric methods which can account for skeletal fragility out of proportion to the degree of bone loss. They are: (i) loss of trabecular connectivity such that vertical weight-bearing bars lose their cross-attachments with each other, thus becoming susceptible to buckling; (ii) inefficient and prolonged microdamage repair due to periods of pause in the formation phase of remodeling; and (iii) accumulation of unrepaired microdamage in unremodeled bone tissue in the central part of trabeculae due to reduced osteon wall thickness coupled with maintenance of trabecular thickness. Recognition of these abnormalities should broaden our approach to the study of skeletal fragility in the syndrome of postmenopausal osteoporosis.     

骨质疏松性脊柱内固定技术进展

骨质疏松症是一种以骨量减少,骨强度下降而脆性增加,骨折风险增加为特征的骨骼疾病。随着人口老龄化日趋严重,骨质疏松症已成为我国面临的重要公共健康问题。这些患者往往并存多种疾病,其中椎体骨折最为突出,危害较大。由于此类患者的虚弱的体质和较低的骨密度,实施手术治疗十分困难。新型的手术方式的开发和内固定植入物的设计明显降低了内固定失败率,提升了内固定稳定性。这些技术综合考虑了生物材料学、生物学和生物力学等多方面,在临床应用上获得了较好的疗效。本综述旨在总结脊柱内固定失败的机制和现存的新型手术技术与内固定植入物设计,并对未来脊柱内固定手术的发展方向加以展望。     

Implications of childhood obesity for adult health: findings from thousand families cohort study

ObjectiveTo determine whether being overweight in childhood increases adult obesity and risk of disease.DesignProspective cohort study.SettingCity of Newcastle upon Tyne.Participants932 members of thousand families 1947 birth cohort, of whom 412 attended for clinical examination age 50.ResultsBody mass index at age 9 years was significantly correlated with body mass index age 50 (r=0.24, P<0.001) but not with percentage body fat age 50 (r=0.10, P=0.07). After adult body mass index had been adjusted for, body mass index at age 9 showed a significant inverse association with measures of lipid and glucose metabolism in both sexes and with blood pressure in women. However, after adjustment for adult percentage fat instead of body mass index, only the inverse associations with triglycerides (regression coefficient= −0.21, P<0.01) and total cholesterol (−0.17, P<0.05) in women remained significant.ConclusionsLittle tracking from childhood overweight to adulthood obesity was found when using a measure of fatness that was independent of build. Only children who were obese at 13 showed an increased risk of obesity as adults. No excess adult health risk from childhood or teenage overweight was found. Being thin in childhood offered no protection against adult fatness, and the thinnest children tended to have the highest adult risk at every level of adult obesity.

What is already known on this topic

Many studies have found that body mass index in childhood is significantly correlated with body mass index in adulthoodObese children have been found to have higher all cause mortality as adults

What this study adds

No excess health risk from childhood overweight was foundChildhood body mass index was linked to adulthood body mass index but not percentage body fatOnly children who were obese at 13 showed a significant increased risk of obesity as adultsPeople who were thinnest as children and fattest as adults tended to have the highest adult risk     

Managing Bone Health in Breast Cancer

ObjectiveOsteoporosis is a common condition that can be caused or exacerbated by estrogen deficiency.MethodsThis narrative review will discuss optimizing bone health in the setting of adjuvant endocrine treatments for hormone receptor–positive breast cancer and the current use of antiresorptive agents as adjuvant therapy and as bone modifying agents.ResultsAdjuvant endocrine treatments for hormone receptor–positive breast cancer (tamoxifen and aromatase inhibitors) affect bone health. The exact effect depends on the agent used and the menopausal state of the woman. Antiresorptive medications for osteoporosis, bisphosphonates and denosumab, lower the risk of bone loss from aromatase inhibitors. Use of bisphosphonates as adjuvant treatment in breast cancer, regardless of hormone receptor status, is increasing because of benefits seen to cancer relapse and survival.ConclusionOptimizing bone health in women with breast cancer during and after cancer treatment is informed by an understanding of breast cancer treatment and its skeletal effect.     

Association Study between the FTCDNL1 (FONG) and Susceptibility to Osteoporosis

Osteoporosis is a systemic skeletal disease characterized by a decreased bone mineral density that results in an increased risk of fragility fractures. Previous studies indicated that genetic factors are involved in the pathogenesis of osteoporosis. Polymorphisms of the FONG (FTCDNL1) gene (rs7605378) were reported to be associated with the risk of osteoporosis in a Japanese population. To assess whether polymorphisms of the FTCDNL1 gene contribute to the susceptibility and severity of osteoporosis in a Taiwanese population, 326 osteoporosis patients and 595 controls of a Taiwanese population were included in this study. Our results indicated that rs10203122 was significantly associated with osteoporosis susceptibility among female. Our findings provide evidence that rs10203122 in FTCDNL1 is associated with a susceptibility to osteoporosis.     

Bone mass, bone strength, and their relationship in developing CD-1 mice

Optimizing nutrition during development may provide effective prevention strategies to protect against osteoporosis during later life. Because the mouse model is commonly used to test nutritional interventions on bone health, the overall objective of this study was to determine how bone develops during the first 4 months of life by assessing bone mass (bone mineral content (BMC) and bone mineral density (BMD)) and biomechanical strength properties such as peak load in male and female CD-1 mice. Bone outcomes were assessed at 1 month intervals from 1 to 4 months of age. Femur and spine BMC and BMD at 3 months were similar to 4 months, indicating that the accumulation of bone mass occurs primarily during the first 3 months of life. In contrast, the timing of changes in peak load, a measure of bone strength, varied by skeletal site. Regression analyses demonstrated that femur BMC is a significant predictor of femur peak load at the femur midpoint and neck. The study findings suggest that nutritional interventions aimed at optimizing peak bone mass to prevent osteoporosis may be most effective during pubertal growth.     

Evaluation and Treatment of Osteoporosis in Patients with a Fragility Hip Fracture

ObjectiveTo determine whether patients with fragility hip fractures underwent assessment and treatment of osteoporosis during initial hospitalization or recommendations for such intervention were made to the primary care provider (PCP) at the time of hospital dismissal.MethodsA review of medical records of patients admitted with a low-impact hip fracture to the Royal University Hospital in Saskatoon, Saskatchewan, Canada, was performed to determine whether recommendations were made to evaluate for or treat osteoporosis. In addition, a questionnaire was sent to the orthopedic surgeons practicing at the hospital to help identify barriers to widespread diagnosis and treatment of osteoporosis in such patients.ResultsBetween January and December 2004, 174 patients with fragility hip fractures were admitted to the Royal University Hospital. The mean age of these patients was 82.5 ± 9.8 years. Evaluation for treatment of osteoporosis was recommended in only 9 patients (5%). We found no significant differences in the intervention rates between male and female patients, between patients with and those without a prior history of osteoporosis or fracture, between patients who were previously taking osteoporosis medications and those who were not, and between patients who were seen by a medical consultant and those who were not. Most orthopedic surgeons believed that they were primarily responsible for the surgical care of these patients, and because they did not see these patients in regular follow-up, the management of osteoporosis was considered the responsibility of the PCP.Conclusion: The results of this study indicate that only a small number of patients with fragility hip fractures receive appropriate evaluation or treatment for underlying osteoporosis either during initial hospitalization or at the time of dismissal from the hospital. In this study, most orthopedic surgeons believed that evaluation and treatment of osteoporosis were the responsibility of the PCP. Because these patients have an increased risk for future fractures, barriers to the diagnosis and treatment of osteoporosis need to be removed, and health-care professionals need to be educated about appropriate risk factor modification in these patients. (Endocr Pract. 2005;11:370-375)     

Association of Childhood Physical and Sexual Abuse with Intimate Partner Violence,Poor General Health and Depressive Symptoms among Pregnant Women

ObjectiveWe examined associations of childhood physical and sexual abuse with risk of intimate partner violence (IPV). We also evaluated the extent to which childhood abuse was associated with self-reported general health status and symptoms of antepartum depression in a cohort of pregnant Peruvian women.MethodsIn-person interviews were conducted to collect information regarding history of childhood abuse and IPV from 1,521 women during early pregnancy. Antepartum depressive symptomatology was evaluated using the Patient Health Questionnaire-9. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).ResultsAny childhood abuse was associated with 2.2-fold increased odds of lifetime IPV (95%CI: 1.72–2.83). Compared with women who reported no childhood abuse, those who reported both, childhood physical and sexual abuse had a 7.14-fold lifetime risk of physical and sexual IPV (95%CI: 4.15–12.26). The odds of experiencing physical and sexual abuse by an intimate partner in the past year was 3.33-fold higher among women with a history of childhood physical and sexual abuse as compared to women who were not abused as children (95%CI 1.60–6.89). Childhood abuse was associated with higher odds of self-reported poor health status during early pregnancy (aOR = 1.32, 95%CI: 1.04–1.68) and with symptoms of antepartum depression (aOR = 2.07, 95%CI: 1.58–2.71).ConclusionThese data indicate that childhood sexual and physical abuse is associated with IPV, poor general health and depressive symptoms in early pregnancy. The high prevalence of childhood trauma and its enduring effects of on women’s health warrant concerted global health efforts in preventing violence.     

Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBDs): What the Endocrinologist Needs to Know

ObjectiveChronic kidney disease-mineral and bone disorders (CKD-MBDs) are a spectrum of abnormalities involving skeletal hormones, minerals, and bone turnover and mineralization. This paper focuses on what the endocrinologist should know about the assessment and management of skeletal and metabolic disorders in CKD-MBDs.MethodsRelevant literature was reviewed to (1) define disturbances of minerals and hormones in the course of CKD; (2) identify the variable radiographic and histomorphometric changes of CKD-MBDs; (3) review the association among CKD-MBDs, vascular calcification, cardiovascular disease (CVD), and mortality; and (4) clarify issues in CKD-MBDs therapy.ResultsAssessment and treatment of CKD-MBDs is complicated by progressive changes in bone minerals and skeletal regulatory hormones as kidney function declines. CKD-MBDs are associated with fracture risk, and studies demonstrate that bone mineral density can be used to assess bone loss and fracture risk in these patients. Treatment of CKD-MBDs continues to evolve. Use of calcium, phosphate binders, vitamin D, vitamin D–receptor analogs, and drugs for osteoporosis and CKD-MBDs treatment are discussed in the context of safety and efficacy for patients with CKD.ConclusionThe association of CKD with bone disease, vascular calcification, CVD, and mortality mandates earlier recognition and treatment of CKD-MBDs. Osteoporosis as a distinct entity can be diagnosed and managed in CKD, although assessment of osteoporosis becomes challenging in late (stage 4 to 5) CKD. Diabetes is common in early (stage 1 to 3) CKD. In addition, 96% of all individuals identified as having CKD have early CKD. The endocrinologist is uniquely positioned to address and treat both diabetes and many of the metabolic and skeletal disorders associated with early CKD-MBDs, including osteoporosis. (Endocr Pract. 2014;20:500-516)     

Long-Term Outcomes Associated with Traumatic Brain Injury in Childhood and Adolescence: A Nationwide Swedish Cohort Study of a Wide Range of Medical and Social Outcomes

BackgroundTraumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated with adult mortality, psychiatric morbidity, and social outcomes.ConclusionsGiven our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents.     

Severe Hypophosphatemic Osteomalacia Secondary to Fanconi Syndrome Due to Adefovir: A Case Report

ObjectiveGeneralized proximal, type 2, renal tubular acidosis, also known as Fanconi syndrome, is a generalized dysfunction of the proximal renal tubule characterized by impaired reabsorption and increased urinary loss of phosphate and other solutes, such as uric acid, glucose, amino acids, and bicarbonate. Chronic hypophosphatemia is the second most common cause of osteomalacia after vitamin D deficiency in adult patients and can have a heterogeneous presentation, ranging from mild symptoms such as muscle weakness and skeletal pain to more severe presentation, such as disabling myopathy, severe bone and joint pain, difficulty walking, and even bone fractures.MethodsThis report describes a case of severe hypophosphatemic osteomalacia with multiple fragility fractures induced by adefovir, which was worsened and confounded by a previous treatment with zoledronic acid and required prolonged intravenous potassium phosphate administration.ResultsWe highlight the limited diagnostic value of dual X-ray absorptiometry and bone scintigraphy in this challenging diagnosis. Bone metabolism should always be assessed in patients treated with adefovir for early detection of osteomalacia due to Fanconi syndrome.ConclusionAlthough rare, this condition may be life-threatening and mimic other bone metabolic disorders that are treated with drugs that may further impair phosphate balance. (Endocr Pract. 2014;20:e246-e249)     

Recommendations on the management of fragility fracture risk in women younger than 70 years

The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for fracture. There are precise diagnostic methods, including a tool to diagnose the risk for fracture. Yet there continues to be an under-diagnosis, with the unrecoverable delay in instituting preventive measures. Women under the age of 70 years, being much more numerous than those older, and having risk factors, are a group in which it is essential to avoid that first fragility fracture. Today it is usual not to differentiate between the treatment and the prevention of osteoporosis since the common aim is to prevent fragility fractures. Included in this are women with osteoporosis or with low bone mass and increased risk for fracture, for whom risk factors play a primary role. There is clearly controversy over the type of treatment and its duration, especially given the possible adverse effects of long-term use. This justifies the concept of sequential treatment, even more so in women under the age of 70, since they presumably will need treatment for many years. Bone metabolism is age-dependent. In postmenopausal women under 70 years of age, the increase in bone resorption is clearly predominant, related to a sharp drop in estrogens. Thus a logical treatment is the prevention of fragility fractures by hormone replacement therapy (HRT) and, in asymptomatic women, selective estradiol receptor modulators (SERMs). Afterwards, there is a period of greater resorption, albeit less intense but continuous, when one could utilise anti-resorptive treatments such as bisphosphonates or denosumab or a dual agent like strontium ranelate. Bone formation treatment, such as parathyroid hormone (PTH), in women under 70 years will be uncommon. That is because it should be used in cases where the formation is greatly diminished and there is a high risk for fracture, something found in much older women.