Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.

Trabecular bone score improves fracture risk assessment in glucocorticoid-induced osteoporosis.

OBJECTIVE: To analyse the clinical utility of trabecular bone score (TBS) evaluation for fracture risk assessment in glucocorticoid (GC)-treated patients compared with BMD assessment. METHODS: One hundred and twenty-seven patients on GC treatment were included [mean age 62 (18) years, 63% women] in this cross-sectional study. The medical history, anthropometric data, lumbar and femoral BMD (DXA) [considering osteoporosis (OP): T-score ⩽-2.5], TBS (considering degraded microarchitecture: <1.230) and dorsolumbar X-ray [to assess vertebral fractures (VF)] were evaluated. BMD and TBS sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were evaluated to determine the diagnostic accuracy of the two methods. RESULTS: All patients were receiving GC treatment for autoimmune diseases during 47.7 (68.9) months at a mean daily dose of 14.5 mg; 17% had VF, 28% any type of fragility fracture (VF + non-VF), 29% OP and 52% degraded microarchitecture. Degraded microarchitecture was significantly more frequent than densitometric OP in patients with VF (76% vs 38%) and with any fragility fracture (69% vs 36%). For VF, TBS and BMD sensitivity, specificity, PPV, and NPV were 0.76, 0.53, 0.25 and 0.92, and 0.38, 0.72, 0.22 and 0.85, respectively. Specificity increased to 0.89 for VF and 0.9 for any fragility fracture on combining BMD+TBS. TBS had better ability than BMD to discriminate between patients with fracture, especially VF (area under the curve = 0.73). CONCLUSION: TBS seems to have greater discriminative power than BMD for fracture risk assessment in GC-treated patients, confirming the utility of this method as a complementary tool in the diagnosis of GC-induced OP.

Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia. / Significado clínico del aumento de los valores séricos de FGF-23 en la displasia fibrosa.

INTRODUCTION AND OBJECTIVE: Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. PATIENTS AND METHODS: Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. RESULTS: FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. CONCLUSION: Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology.

Bone disease in patients awaiting liver transplantation. Has the situation improved in the last two decades?

In recent years, there has been speculation about the possibility of a reduction in the incidence of fractures after liver transplantation (LT) because of changes in the characteristics of candidates and the use of different immunosuppressive therapies. We analyzed the characteristics of LT candidates (CTC) and compared them with historical data from a group of LT candidate patients (HTC). Data from 60 CTC patients consecutively included in a screening program of metabolic bone disease were compared with data from 60 HTC patients prospectively evaluated between 1992 and 1993. In all patients, we analyzed the clinical and laboratory characteristics, bone mineral density (BMD) dual-energy X-ray absorptiometry, and skeletal fractures. Patients in the CTC group were older than patients in the HTC group. The CTC group had lower femoral neck T scores. No differences were observed between groups in the proportion of patients with osteoporosis (22 vs. 30 %, p = ns) or fractures (36 vs. 33 %, p = ns). The percentage of patients with normal BMD decreased from 38 to 20 %. 25(OH)D values were low in both groups. Only 7.5 % of the CTC patients received calcium and/or vitamin D supplementation. The prevalence of fractures among CTC patients was similar to that seen two decades ago. At present, candidates for LT are older and have lower femoral bone mass. Vitamin D deficiency remains frequent; however, calcium and/or vitamin D supplementation is uncommon.

Osteoporosis en la cirrosis hepática / Osteoporosis in liver cirrhosis

La osteoporosis es una complicación frecuente en la enfermedad hepática crónica, especialmente en las etapas finales de la enfermedad. El problema es más crítico en los pacientes trasplantados, cuando la pérdida ósea se acelera durante el período inmediatamente después de la cirugía. El principal mecanismo implicado en el desarrollo de osteoporosis en los hepatópatas es el déficit de la formación ósea, por el efecto nocivo de sustancias como la bilirrubina y los ácidos biliares, o bien por el efecto tóxico del alcohol o el hierro sobre los osteoblastos.Para la prevención y el tratamiento de la osteoporosis es recomendable una buena nutrición y la administración de suplementos de calcio y vitamina D. No hay pautas concretas en su tratamiento farmacológico, pero se ha demostrado que los bisfosfonatos son eficaces para aumentar la masa ósea en pacientes con colestasis crónica, con un buen perfil de seguridad (AU)

Osteoporosis is a common complication of chronic liver disease, especially in the final stages. This entity is more critical in liver transplant recipients, when bone loss accelerates during the immediate postoperative period. The main mechanism involved in the development of osteoporosis in liver disease is deficient bone formation due to the harmful effects of substances such as bilirubin and bile acids or the toxic effect of alcohol or iron on osteoblasts.To prevent and treat osteoporosis, good nutrition and calcium and vitamin D supplementation are required. There are no specific recommendations on drug treatment but bisphosphonates are effective in increasing bone mass in patients with chronic cholestasis and have a good safety profile (AU)

25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis.

UNLABELLED: It remains unclear whether vitamin D sufficiency optimizes response to bisphosphonate (BP) treatment in postmenopausal osteoporosis. We evaluated the role and possible mechanisms of vitamin D in adequate response to standard BP treatment for postmenopausal osteoporosis. METHODS: We included 120 postmenopausal osteoporotic women (aged 68 ± 8 years) receiving BP (alendronate or risedronate) at their annual follow-up, performing complete anamnesis, including treatment adherence, use of vitamin D supplements, and previous falls and fractures during the last year. We analyzed the evolution of bone mineral density (BMD) during this period and serum PTH and 25 hydroxyvitamin D (25(OH)D) and urinary NTx levels. Patients were classified as inadequate responders to antiosteoporotic treatment based on BMD loss>2% and/or the presence of fragility fractures during the last year. RESULTS: Thirty percent of patients showed inadequate response to BP treatment, with significantly lower levels of 25(OH)D (22.4 ± 1.3 vs. 26.6 ± 0.3 ng/ml, p=0.01), a higher frequency of 25(OH)D levels<30 ng/ml (91% vs. 69%, p=0.019) and higher urinary NTx values (42.2 ± 3.9 vs. 30.9 ± 2.3 nM/mM, p=0.01). Patients with 25(OH)D>30 ng/ml had a greater significant increase in lumbar BMD than women with values <30 ng/ml (3.6% vs. 0.8%, p<0.05). The probability of inadequate response was 4-fold higher in patients with 25(OH)D<30 (OR, 4.42; 95% CI, 1.22-15.97, p=0.02). CONCLUSIONS: Inadequate response to BP treatment is frequent in postmenopausal women with osteoporosis as is vitamin D insufficiency, despite vitamin D supplementation. Maintenance of 25(OH)D levels >30 ng/ml is especially indicated for adequate response to BP treatment.

[Osteoporosis in liver cirrhosis]. / Osteoporosis en la cirrosis hepática.

Osteoporosis is a common complication of chronic liver disease, especially in the final stages. This entity is more critical in liver transplant recipients, when bone loss accelerates during the immediate postoperative period. The main mechanism involved in the development of osteoporosis in liver disease is deficient bone formation due to the harmful effects of substances such as bilirubin and bile acids or the toxic effect of alcohol or iron on osteoblasts. To prevent and treat osteoporosis, good nutrition and calcium and vitamin D supplementation are required. There are no specific recommendations on drug treatment but bisphosphonates are effective in increasing bone mass in patients with chronic cholestasis and have a good safety profile.

Management of osteoporosis in liver disease.

Osteoporosis resulting in a high risk for fracture is a common complication in patients with liver disease, particularly in those with chronic cholestasis and with end-stage cirrhosis. The pathogenesis of bone loss in liver patients is poorly understood but it mainly results from low bone formation as a consequence of cholestasis or the harmful effects of alcohol or iron on osteoblasts. Increased bone resorption has also been described in cholestatic women with advanced disease. The management of bone disease in liver patients is addressed to reduce or avoid the risk factors for osteoporosis and fracture. Bisphosphonates associated with supplements of calcium and vitamin D are safe and effective for increasing bone mass in patients with chronic cholestasis and after liver transplantation, though no clear achievements in descreasing the incidence of fractures have been described, probably because of the low number of patients included in the therapeutic trials. Randomized studies assessing bisphosphonates in larger series of patients, the development of new drugs for osteoporosis and the improvement in the management of liver transplant recipients may change the future.

Liver and bone.

Osteoporosis is a frequent complication in patients with chronic liver disease, especially in end-stages and in cases with chronic cholestasis, hemochromatosis and alcohol abuse. The problem is more critical in transplant patients when bone loss is accelerated during the period immediately after transplantation, leading to a greater incidence of fractures. Advanced age, low body mass index and severity of the liver disease are the main risk factors for bone disease in patients with cholestasis. Mechanisms underlying osteoporosis in chronic liver disease are complex and poorly understood, but osteoporosis mainly results from low bone formation, related to the effects of retained substances of cholestasis, such as bilirubin and bile acids, or to the effects of alcohol on osteoblastic cells. Increased bone resorption has also been described in cholestatic women with advanced disease. Although there is no specific treatment, bisphosphonates associated with supplements of calcium and vitamin D are effective for increasing bone mass in patients with chronic cholestasis and after liver transplantation. The outcome in reducing the incidence of fractures has not been adequately demonstrated essentially because of the low number of patients included in the therapeutic trials. Randomized studies assessing bisphosphonates in larger series of patients, the development of new drugs for osteoporosis and the improvement in the management of liver transplant recipients may change the future.

Prevalence of vertebral fracture in postmenopausal women with lumbar osteopenia using MorphoXpress® (OSTEOXPRESS Study).

BACKGROUND AND AIMS: Vertebral fracture (VF) is the most common complication of osteoporosis. However, more than half of all VF are asymptomatic and may go unnoticed, even in patients with osteoporosis. Our aim was to assess the prevalence of VF in postmenopausal women with osteopenic lumbar densitometry by means of vertebral morphometry, using the MorphoXpress® software. PATIENTS AND METHODS: This was an epidemiological, cross-sectional, multicenter study conducted among 289 postmenopausal women (>1 year of amenorrhoea), diagnosed with lumbar osteopenia (not due to chronic treatment with corticosteroids or immobilization). Vertebral deformities ≥20% were considered as VF. RESULTS: Demographic and clinical characteristics showed mean age (±SD) 64±9 years, body mass index 27±5 kg/m2, and time from diagnosis of 2±3 years. A total of 25% of subjects had a family history of osteoporotic fracture in first-degree relatives, and 23% had previous fragility fracture. The prevalence of VF was 50% (CI 95% 44-56), the most frequent being the dorsal wedge (34%). Previous fragility fracture was a risk factor for VF (OR 3.13, p=0.0004). A total of 76.5% of patients were receiving treatment, mainly calcium and vitamin D supplements (70%) and bisphosphonates (27%). CONCLUSIONS: MorphoXpress® revealed that 50% of postmenopausal women with osteopenic lumbar densitometry showed VF. This result is important since only 7% of all evaluated subjects had previously been diagnosed with VF.

Bone mineral density evolution in young premenopausal women with idiopathic osteoporosis.

Idiopathic osteoporosis is a frequent cause of osteoporosis in young premenopausal women. However, there are no data about the treatment of these patients. The aim of this study was to analyse the evolution of bone mineral density (BMD) in premenopausal women with idiopathic osteoporosis treated with a conservative approach. Retrospective study of 16 premenopausal women with idiopathic osteoporosis (aged 35.7+/-7 years) with a mean follow-up period of 3 years (1-6 years). BMD measurements at the lumbar spine and femoral neck were obtained in all patients at baseline and yearly (patients had one or more fragility fractures and/or a Z score < -2 in the lumbar spine or femur). Secondary causes of osteoporosis were excluded in all patients. Patients were treated with calcium and vitamin D to achieve a calcium intake of up to 1,500 mg/day and were advised to increase physical activity. A significant increase in lumbar and femoral BMD was observed after 2 and 3 years of follow-up, respectively (1.9+/-1.9% mean increase in lumbar spine, p= 0.021, at 2 years) (5.6+/-4.5% mean increase in femur, p=0.04, at 3 years). The serum total alkaline phosphatase (TAP) values increased at 2 years (122+/-46 vs 140+/-36 U/l, p=0.054). In addition, a negative correlation between baseline TAP serum values and lumbar BMD evolution at 2 years was observed (r=-0.748, p=0.013). No patient developed new skeletal fractures during the follow-up period. In young premenopausal women with idiopathic osteoporosis the conservative treatment with supplements of calcium and vitamin D associated with an increase of physical activity is associated with an increase in BMD without evidence of further skeletal fractures after more than 3 years of follow-up.