Significant Increase In Bone Mineral Density Research Articles

Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy

Limited data have been reported on the effect of parathyroidectomy (PTx) on bone mineral density (BMD) in the setting of patients with hyperparathyroidism (HPT) associated with multiple endocrine neoplasia type 1 (MEN1). This study investigates the impact of total PTx on BMD in patients with HPT/MEN1. A case series study was performed in a tertiary academic hospital. A total of 16 HPT/MEN1 patients from six families harbouring MEN1 germline mutations were subjected to total PTx followed by parathyroid auto-implant in the forearm. Bone mineral density values were assessed using dual-energy X-ray absorptiometry. Before PTx, reduced BMD (Z-score <-2.0) was highly prevalent in the proximal one-third of the distal radius (1/3 DR) (50%), lumbar spine (LS) (43.7%), ultradistal radius (UDR) (43.7%), femoral neck (FN) (25%) and total femur (TF) (18.7%) in the patients. Fifteen months after PTx, we observed a BMD improvement in the LS (from 0.843 to 0.909 g/cm(2); +8.4%, P = 0.001), FN (from 0.745 to 0.798 g/cm(2); +7.7%, P = 0.0001) and TF (from 0.818 to 0.874 g/cm(2); +6.9%, P < 0.0001). No significant change was noticed in the 1/3 DR and UDR after PTx. This data confirmed BMD recovery in the LS and FN after PTx in HPT/MEN1 patients. We also documented a significant BMD increase in the TF and no change in both the 1/3 DR and UDR BMD after PTx. Our data suggest that LS and proximal femur are the most informative sites to evaluate the short-term BMD outcome after PTx in HPT/MEN1 subjects.

Bone remodeling in proximal HA-coated versus uncoated cementless SL-Plus® femoral components: a 5-year follow-up study

Bone resorption at the femoral stem due to stress shielding has been particularly observed secondary to cementless hip replacement. This prospective study of 126 total-hip replacements was performed to examine clinical outcomes and changes in peri-prosthetic bone density after implantation of a double-tapered cementless femoral component manufactured with versus without hydroxyapatite (HA) coating. Sixty-seven femoral components with and 59 femoral components without proximal HA coating were implanted and examined after a mean follow-up of 5.8 (SD 1.1, 2.8-7.8) years. The Harris hip score (HHS) and plain radiographs were used for clinical and radiological follow-up evaluations. Possible changes in peri-prosthetic bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DEXA). Clinical outcome, measured by HHS, was similar in both groups. On plain radiographs, significantly less radiolucent lines were observed for the coated implants. DEXA revealed a significant increase in BMD at the proximal zones, along the medial side, and at the stem tips in the coated compared with the non-coated implants. Hydroxyapatite-coated implants yield favorable radiographic characteristics, but no greater clinical benefit after 5 years' implantation.

The effects of weekly alendronate therapy in Taiwanese males with osteoporosis

The aim of this study was to evaluate the efficacy, safety, and tolerability of weekly alendronate administration on male osteoporosis in Taiwan. This 6-month, randomized, open-label controlled trial enrolled 46 men with osteoporosis who were randomized to either 70 mg alendronate once weekly (n = 23) or control (n = 23). Bone mineral density (BMD) of lumbar spine and hip and biochemical bone turnover markers were measured; adverse events and tolerability were assessed. Subjects treated with alendronate showed a significant increase in BMD of 5.5% (vs. 2% in control group) at the lumbar spine and 2.7% (vs. 0.7%) at the femoral neck (P < 0.05) at 6 months, respectively. There were also significant decreases in serum level of bone formation marker (bone-specific alkaline phosphatase) and urinary excretion of bone resorption marker (deoxypyridinoline) at 3 and 6 months. Thus, alendronate showed anti-osteoporotic effects by increasing BMD and decreasing the concentrations of bone markers. The adverse events were mild and showed no significant difference between the two groups on safety assessments.

Local Soft Tissue Compression Enhances Fracture Healing in a Rabbit Fibula

Local soft tissue compression of fractures enhances fracture healing. The mechanism remains uncertain. Past studies have focused on intermittent soft tissue compression. We report a preliminary study assessing the relationship between constant soft tissue compression and enhanced fracture healing in an osteotomy model designed to minimize confounding variables. Fibulae of nine New Zealand white rabbits were bilaterally osteotomized, openly stabilized, and fitted with spandex stockinets. Soft tissue at the osteotomy site was unilaterally compressed using a deforming element (load = 26mmHg). The contralateral side was saved as the control and was not compressed. Osteotomies were monitored with weekly radiographs. All fibulae in both groups were healed 6weeks postoperatively. Micro-CT analysis of bone mineral density (BMD) and bone volume (BV) was then performed on both the experimental and control sides. Radiographic measurement of transverse callus-to-shaft ratios (TCSR) was compared. BMD of the experimental callus was greater than the noncompressed controls. BV and TCSR were not different between controls and experimental osteotomies. Constant local soft tissue compression produced significant increases in BMD, but not in BV or transverse callus size, indicating significant measurable increases in callus composition without significant change in gross dimensions. Our experimental design minimizes confounding factors, such as micromotion, immobilization, and altered venous flow, suggesting that these are not the primary mechanisms for fracture healing enhancement. Further studies with more animals and study groups are necessary to confirm efficacy and identify optimal compression pressures and schedules.

Alendronate decreases the fracture risk in patients with prostate cancer on androgen‐deprivation therapy and with severe osteopenia or osteoporosis

To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen-deprivation therapy (ADT) and with a basal T-score of >-2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture. We selected 61 patients with prostate cancer treated with ADT; 31 were treated with oral alendronate 70 mg once-weekly and a control group of 30 were not. At baseline and 12 months we measured bone mineral density (BMD) of the lumbar spine, femoral neck and total hip by dual-energy X-ray absorptiometry. All patients had severe osteopenia or osteoporosis at baseline. The risk of femoral neck fracture was calculated at baseline and 12 months (Z-score 2.7). Patients treated with alendronate had a significant increase in BMD at the lumbar spine and femoral neck after 1 year of follow-up, with mean (sd) values of 1.06 (0.26) vs 1.01 (0.21) g/cm(2) at baseline (P < 0.001), and 0.75 (0.07) vs 0.73 (0.07) g/cm(2) (P = 0.03), respectively, while the control group had a significant loss of BMD at the total hip of 0.79 (0.14) vs 0.81 (0.13) g/cm(2) (P = 0.03). BMD was significantly improved at the three locations in patients treated with alendronate compared with the control group, with differences at the lumbar spine, femoral neck and total hip of 0.05 (0.07) vs 0.01 (0.10) (P = 0.001), 0.01 (0.04) vs -0.002 (0.03) (P = 0.04) and 0.01 (0.04) vs -0.01 (0.02) g/cm(2), respectively (P = 0.001). Patients treated with alendronate had a significant decrease in the fracture risk at the femoral neck, by -0.54 (1.29) (P = 0.04) after 1 year of follow-up. Treatment with once-weekly 70 mg alendronate significantly improved the BMD at the lumbar spine and femoral neck in patients with prostate cancer with severe osteopenia or osteoporosis and on ADT, and significantly decreased the risk of femoral neck fracture.

Prevention of Osteoporosis. Four-Year Follow-Up of a Cohort of Postmenopausal Women Treated with an Ossein-Hydroxyapatite Compound

Background: The long-term effects of ossein-hydroxyapatite compound (OHC), a drug used for osteoporosis prevention, have not been previously reported. The aim of this study was to assess the long-term efficacy of OHC in postmenopausal women with bone mineral density (BMD) in the osteopenia range. Methods: We performed a retrospective 4-year follow-up study in a primary-care setting to assess changes in BMD in a cohort of 112 postmenopausal women included in an osteoporosis programme that included health and dietary advice and who were treated with OHC 1660mg every 12 hours. BMD was measured annually in the distal part of the forearm, with T- and Z-score values being calculated for trabecular and total bone. Results: A progressive and statistically significant increase in BMD was observed in trabecular and total T- and Z-score mean values. At baseline, mean ±SD trabecular T- and Z-scores were –1.27±0.7 and –1.03±0.7, respectively, and –0.86±0.7 and –0.62±0.7, respectively, at the end of the 4-year follow-up period (both p &lt; 0.0001). Mild constipation was observed in 3.2% of patients during the follow-up period. Conclusion: Ossein-hydroxyapatite compound could be an effective and safe agent for the prevention of bone loss in postmenopausal osteopenic women, with significant increases in BMD being observed in this group of patients.

High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1

Although it is known that neurofibromatosis 1 (NF1) patients suffer from vitamin D deficiency and display decreased bone mineral density (BMD), a systematic clinical and histomorphometrical analysis is absent. Our data demonstrate that NF1 patients display high bone turnover and accumulation of osteoid and that supplementation of vitamin D has a beneficial effect on their BMD. Neurofibromatosis 1 results in a wide range of clinical manifestations, including decreased BMD. Although it has been reported that NF1 patients have decreased vitamin D serum levels, the manifestation of the disease at the bone tissue level has rarely been analyzed. Thus, we performed a clinical evaluation of 14 NF1 patients in comparison to age- and sex-matched control individuals. The analysis included dual X-ray absorptiometry osteodensitometry, laboratory parameters, histomorphometric and quantitative backscattered electron imaging (qBEI) analyses of undecalcified bone biopsies. NF1 patients display significantly lower 25-(OH)-cholecalciferol serum levels and decreased BMD compared to control individuals. Histomorphometric analysis did not only reveal a reduced trabecular bone volume in biopsies from NF1 patients, but also a significantly increased osteoid volume and increased numbers of osteoblasts and osteoclasts. Moreover, qBEI analysis revealed a significant decrease of the calcium content in biopsies from NF1 patients. To address the question whether a normalization of calcium homeostasis improves BMD in NF1 patients, we treated four patients with cholecalciferol for 1 year, which resulted in a significant increase of BMD. Taken together, our data provide the first complete histomorphometric analysis from NF1 patients. Moreover, they suggest that low vitamin D levels significantly contribute to the skeletal defects associated with the disease.

Efeitos da natação e do treinamento resistido na densidade mineral óssea de mulheres idosas

Exercícios com impacto como caminhada, saltos, corridas e exercícios resistidos são muito utilizados para prevenção da perda óssea em idosas. No entanto, poucos são os estudos que relatam os efeitos da natação na manutenção da massa óssea em mulheres idosas. Portanto, o objetivo deste estudo foi comparar os efeitos da natação com o treinamento resistido na densidade mineral óssea (DMO) de mulheres idosas. Vinte e três mulheres com idade média de 63,9 ± 6,49 anos foram divididas em dois grupos: 1) grupo natação (NAT, n = 13, que) treinou em intensidade entre 60 e 90% da freqüência cardíaca de reserva; 2) grupo treinamento resistido (TR, n = 10), que treinou os principais grupamentos musculares com três séries a 80% de 1RM. Os dois grupos praticaram três vezes por semana com uma hora de duração para cada sessão, durante seis meses. A DMO do colo do fêmur e da coluna lombar (L2-L3-L4) foi mensurada através de DXA antes (T0) e após seis meses de treino (T6). Os resultados mostraram que as médias para a DMO lombar em T0 (0,9250 ± 0,1506g/cm²) e T6 (0,9303 ± 0,1269g/cm²) para o NAT e em T0 (0,9739 ± 0,1249g/cm²) e T6 (0,9737 ± 0,1317g/cm²) para o TR não foram diferentes quando comparadas intra ou intergrupos. De modo similar, não houve diferenças entre a DMO do colo do fêmur em T0 (0,7784 ± 0,1523g/cm²) e T6 (0,7905 ± 0,1610g/cm²) para o NAT e T0 (0,7546 ± 0,1360g/cm²) e T6 (0,7522 ± 0,1421g/cm²) para o TR. Os resultados deste estudo não demonstraram diferenças na DMO entre NAT e TR após seis meses de treino; e que tanto TR quanto NAT não produzem aumentos significativos na DMO de mulheres idosas nesse período.

Running Exercise for Short Duration Increases Bone Mineral Density of Loaded Long Bones in Young Growing Rats

Running exercise is an effective therapy for the prevention of osteoporosis; however, appropriate duration of exercise has not been determined. We therefore investigated the effect of exercise duration on bone mineral density (BMD) and systemic bone metabolism using young growing rats. Fifteen 8-week-old female Wistar rats were divided into three groups according to running load: control group (no running), short duration (30 min/day) and long duration (180 min/day), and animals ran on a treadmill 5 days per week over an 8-week period. BMD of the tibia was measured using peripheral quantitative computed tomography, and serum levels of tartarate-resistant acid phosphatase (TRAP), a bone resorption marker and alkaline phosphatase (ALP), a bone formation marker were measured to know whether the treadmill exercise would affect systemic bone metabolism. Short-duration running exercise (30 min/day) caused a significant increase in BMD of the metaphyseal trabecula (p < 0.05) with a reduction of serum TRAP levels (p < 0.01) and an increase in serum levels of calcium (p < 0.05) and phosphorus (p < 0.01). Conversely, long-duration exercise (180 min/day) significantly reduced BMD of the diaphyseal and metaphyseal cortex and that of the diaphyseal trabecula with a significant reduction of serum ALP levels and a significant increase in serum phosphorus. These findings suggest that short-duration exercise may increase BMD through suppression of bone resorption, whereas long-duration exercise may reduce BMD through suppression of bone formation. Exercising for short duration but not prolonged exercise is recommended to increase BMD of loaded long bones.

A Comparison of Calcium, Calcitriol, and Alendronate in Corticosteroid-Treated Premenopausal Patients with Systemic Lupus Erythematosus

To assess bone mineral density (BMD) changes in patients with systemic lupus erythematosus (SLE) undergoing longterm therapy with corticosteroids (CS) while taking calcium, calcitriol, or alendronate. The primary endpoint was BMD changes at 2 years. Premenopausal SLE patients were randomized into 3 groups according to medication: calcium carbonate 500 mg bd (calcium alone), calcitriol 0.25 microg bd plus calcium carbonate 500 mg bd (calcitriol + calcium), and alendronate 70 mg/week plus calcium carbonate 500 mg bd (alendronate + calcium). BMD was measured at baseline and at the end of the first and second years. Ninety-eight patients were recruited. There were 33 patients taking calcium alone, 33 calcitriol + calcium, and 32 alendronate + calcium. On randomization, median duration of CS use was 2.5 years (range 0-20 yrs). Seventy-seven patients (78.6%) completed the study (23 taking calcium alone, 27 calcitriol + calcium, 27 alendronate + calcium). There were no significant differences in mean CS dosages among the 3 groups at the time of BMD measurements. After 2 years, there were no significant changes in BMD in the calcium-alone and calcitriol + calcium groups, apart from a 0.93% (p < 0.001) reduction in total hip BMD in the calcium-alone group. In contrast, the alendronate + calcium group showed significant increases in BMD of 2.69% (p < 0.001) in the lumbar spine and 1.41% (p < 0.001) in total hip. Both calcium alone and calcitriol + calcium preserved lumbar spine BMD in premenopausal patients with SLE taking longterm CS at 2 years, whereas alendronate + calcium led to increases in BMD in lumbar spine and total hip. Premenopausal women taking CS should be considered for osteoporosis prophylaxis.

The Effects of Strontium Ranelate in Asian Women with Postmenopausal Osteoporosis

The aim of this study was to assess the efficacy and safety of strontium ranelate in the treatment of postmenopausal women with osteoporosis in Taiwan. In this 12-month multicenter, randomized, double-blind, placebo-controlled study, 125 women with osteoporosis were randomly given either strontium ranelate 2 g daily or placebo. Lumbar spine, femoral neck, and total-hip bone mineral density (BMD) and biochemical markers of bone turnover were measured; adverse events and tolerability were recorded and assessed. Subjects treated with strontium ranelate showed significant increases in BMD of 5.9% at the lumbar spine, 2.6% at the femoral neck, and 2.7% at the total hip, while the placebo group exhibited no significant change at 12 months. Serum level of a formation marker (bone-specific alkaline phosphatase) was also significantly increased at 6 and 12 months. Thus, although the sample size and the treatment duration of this study could not show its effect of reducing osteoprotic fractures, strontium ranelate showed bone protection effects by increasing BMD and concentrations of a bone formation marker. Safety assessment revealed adverse events were mild and not significantly different from placebo.

Randomized Trial of Denosumab in Patients Receiving Adjuvant Aromatase Inhibitors for Nonmetastatic Breast Cancer

Adjuvant aromatase inhibitor therapy is well established in postmenopausal women with hormone receptor-positive breast cancer, but such therapy is complicated by accelerated bone loss and increased fracture risk. We investigated the ability of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, to protect against aromatase inhibitor-induced bone loss. Eligible women with hormone receptor-positive nonmetastatic breast cancer treated with adjuvant aromatase inhibitor therapy were stratified by duration of aromatase inhibitor therapy (< or = 6 v > 6 months), received supplemental calcium and vitamin D, and were randomly assigned to receive placebo (n = 125) or subcutaneous denosumab 60 mg (n = 127) every 6 months. At enrollment, all patients were required to have evidence of low bone mass, excluding osteoporosis. The primary end point was percentage change from baseline at month 12 in lumbar spine bone mineral density (BMD). At 12 and 24 months, lumbar spine BMD increased by 5.5% and 7.6%, respectively, in the denosumab group versus placebo (P < .0001 at both time points). Increases were observed as early as 1 month and were not influenced by duration of aromatase inhibitor therapy. Increases in BMD were also observed at the total hip, total body, femoral neck, and the predominantly cortical one-third radius. Bone turnover markers decreased with denosumab treatment. Overall incidence of treatment-emergent adverse events (AEs) was similar between treatment groups. In women with nonmetastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy, twice-yearly administration of denosumab led to significant increases in BMD over 24 months at trabecular and cortical bone, with overall AE rates similar to those of placebo.

Bisphosphonate-laden acrylic bone cement: Mechanical properties, elution performance, andin vivoactivity

Cemented total hip replacements generally fail after 10-20 years, often due to implant loosening from bone resorption. Bisphosphonates such as zoledronic acid (ZA) and pamidronate (PAM) are potent inhibitors of bone resorption. The local delivery of bisphosphonates via acrylic bone cement could decrease osteolysis and prolong implant lifespan. Conflicting studies suggest that bisphosphonate loading may or may not reduce the mechanical properties of acrylic bone cement. We assayed acrylic bone cement laden with ZA or PAM at different concentrations and diluent volumes. Four-point bend testing and compressive testing indicated that high volumes of diluent (with or without bisphosphonate) significantly reduced bending modulus and compressive strength. Radiography and electron microscopy indicated that high diluent volumes generated abnormal acrylic bone cement structure. After 6 weeks of incubation in saline, only 0.9% w/w of the total bisphosphonate incorporated in acrylic bone cement eluted in vitro, indicating a slow elution rate. In vivo testing was performed using a rat model. Cement cylinders were inserted into incisions in rat distal femora and ZA delivered locally (via elution from acrylic bone cement) or systemically (via injection). At 4 weeks postoperatively, dual energy X-ray absorptiometry demonstrated no significant increase in local bone mineral density (BMD) adjacent to ZA-laden implants. In contrast, systemic ZA delivery (0.1 mg/kg) led to a large (48.6%) and significant increase in BMD. Thus, systemic delivery appears more effective than local delivery.

Use of monthly oral ibandronate to prevent anastrozole-induced bone loss during adjuvant treatment for breast cancer: Two-year results from the ARIBON study

554 Background: The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in postmenopausal women taking adjuvant anastrozole for their endocrine responsive breast cancer. Methods: BMD was assessed in 131 patients prior to commencing adjuvant endocrine treatment. 68, 50, and 13 patients were found to be normal (T >-1.0, group 1), osteopenic (T -1.0 to -2.5, group 2), and osteoporotic (T <-2.5, group 3), respectively. All patients were treated with anastrozole 1mg once a day and calcium and vitamin D supplementation. In addition, group 2 patients were randomized on a 1:1 basis to receive either treatment with oral ibandronate 150 mg every month or placebo. Group 3 patients were treated with open label oral ibandronate 150mg every month. BMD and bone marker measurements were repeated at regular intervals for two years. Group 1 patients were followed up on calcium and vitamin D supplements alone. Results: BMD changes in groups 2 and 3 are shown in the table. In group 2 the mean difference in percentage BMD changes between the ibandronate and placebo treated patients after 1 and 2 years was 5.5 and 6.2% (95% CI 2.4–10.0) at the lumbar spine (LS) and 3.2 and 4.5% (95% CI 1.7–7.3) at the hip (TH) (p<0.01, independent samples t test). After 1-year Urinary n-telopeptide (uNTX), serum c-telopeptide (sCTX), and serum bone-specific alkaline phosphatase (sBALP) levels declined in patients receiving ibandronate (21, 26, and 23%, respectively) and increased in those taking placebo (40, 35, and 40%, respectively). Biomarker assessments at 2 years are ongoing. As expected, group 1 patients lost 4.8% (range -13.8, +4.5) at the LS and 3.7% (range -15.9, +1.3) at the TH after 2 years. Conclusions: Ibandronate 150 mg by mouth once a month prevents anastrozole-induced bone loss and results in significant increases in BMD at the LS and TH in osteopenic and osteoporotic patients. Mean Percentage Change in BMD (Ranges) Osteopenia Osteoporosis Ibandronate Placebo Ibandronate 1 yr n=23 2 yr n=21 1 yr n=25 2 yr n=19 1 yr n=12 2 yr n=12 LS +3.11 (-3.8, +15.1) +2.98 (-8.9, +19.9) -2.35 (-10.5, +2.2) -3.22 (-16.0, +4.3) +5.02 (-8.7, +15.2) +3.52 (-4.9, +14.6) TH +0.98 (-4.1, +5.6) +0.60 (-9.0, +6.9) -2.27 (-9.9, +5.2) -3.90 (-12.3, +7.2) +2.90 (-1.0, +8.5) +2.49 (-3.7, +8.1) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology, Roche AstraZeneca Oncology

Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women

Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival. This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD. This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America. Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5. SUBJECTS were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (< or =5 yr or > 5 yr). The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety. Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups. Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.

Significance of a decline in bone mineral density while receiving oral bisphosphonate treatment

Background: Oral bisphosphonates are routinely prescribed for the treatment of postmenopausal osteoporosis. In clinical trials, oral bisphosphonates have been found to increase bone mineral density (BMD) and decrease fracture risk in the majority of the treated population. However, in both clinical trials and clinical practice, not all patients experience significant increases in BMD. In clinical trials, nonresponse is often defined as a BMD change of ≤0%. In clinical practice, a decrease in BMD greater than the calculated least significant change (LSC) is considered nonresponse to therapy. It is important to discern whether patients with a decline in BMD may still benefit from oral bisphosphonate therapy, that is, have a reduced risk for fracture, despite having a suboptimal BMD response. Objectives: The objectives of this review were to determine whether meaningful BMD nonresponder rates exist with all oral bisphosphonates and to examine the relationship between BMD nonresponder status and fracture risk. Finally, we discuss the potential implications of BMD nonresponse for patients in clinical practice. Methods: Publications on BMD response and bone loss during treatment with bisphosphonates were identified by searches of MEDLINE (1990-October 2007) and ISI Web of Science (1997-October 2007). Search terms included nonresponse, responder, osteoporosis, bone mineral density, bisphosphonate, alendronate, risedronate, ibandronate, bone loss, and fracture. Results: In clinical trials of alendronate, risedronate, and ibandronate, the percentages of patients with a change in BMD ≤0% at the lumbar spine after 2 years of treatment ranged from 8% to 25%. Results from post hoc analyses of clinical trial data from studies of alendronate and risedronate that have examined fracture risk among BMD responders, BMD nonresponders, and patients receiving placebo suggest that patients who experienced an increase in BMD have reduced vertebral fracture risk relative to those with a decline in BMD (range, 38%-50%). Additional analyses suggest that patients who experience a decline in BMD while receiving oral bisphosphonate therapy still appear to receive some benefit (fracture risk reduction, 38%-60%) from treatment compared with patients receiving placebo. Conclusions: Results from post hoc analyses of clinical trial data suggest that patients receiving oral bisphosphonate therapy who experience a decline in BMD have a higher risk for fracture compared with patients whose BMD increases, but may have a reduced fracture risk compared with patients receiving placebo. Further investigation is needed to determine how these results impact patients in clinical practice whose BMD loss exceeds the LSC.

Effects of salmon calcitonin in treatment of osteoporosis in patients undergoing dialysis

To investigate the prevalence of osteoporosis in patients undergoing maintenance dialysis and explore the safety and efficacy of salmon calcitonin in maintenance dialysis patients underwent with osteoporosis. Double-energy X-ray bone density meter was used on 256 patients undergoing maintenance dialysis, 126 males and 130 females, aged 60 +/- 14 (22 -79), to measure the bone mineral density (BMD) at the lumbar spine and femoral neck. 108 of them with the T values < -2.5 s were diagnosed as with osteoporosis, and then were randomly divided into 2 equal groups matched in baseline age, sex, mode of dialysis, and levels of iPTH, ALP, and BMD: control group receiving oral administration of calcium carbonate 1500 mg tid and rocaltrol 0.25 microg qn for 18 months, and experimental group, received subcutaneous injection of salmon calcitonin (50 U) three times a week in addition. The BMD levels of lumbar spine and femoral neck, and serum intact parathyroid hormone (iPTH), calcium, phosphorus, and alkaline phosphatase (ALP) were assessed before treatment and 3, 6, 12, and 18 months after treatment. (1) The osteoporosis rate of the 256 maintenance dialysis patients was 42.19%. (2) The osteoporosis rate of the 201 patients undergoing maintenance hemodialysis (MHD) was 47.76%, significantly higher than that of the 55 patients undergoing maintenance peritoneal dialysis (21.82%, P < 0.01). (3) At the end of the trial, there was a significant increase of BMD of lumbar spine and femoral neck in the experiment group compared with the control group. (4) Compared with the control group, the serum ALP, iPTH, and BGP levels 3, 6, 12, and 18 months after treatment were all significantly lower than the baseline level and those of the corresponding control groups (all P < 0.01). The serum calcium of the control group at the end of experiment increased significantly in comparison with baseline level (P < 0.05). (5) No adverse events were found after the treatment of salmon calcitonin. Salmon calcitonin effectively increases the BMD of the maintenance dialysis patients and is well tolerated.

Bone Mineral Density Before and After Surgical Cure of Cushing’s Syndrome Due to Adrenocortical Adenoma: Prospective Study

Osteoporosis is a major complication of Cushing's syndrome. The aim of the present study was to assess the chronologic effect of surgical cure on bone mineral density (BMD) in patients with Cushing's syndrome due to adrenal adenoma. BMD was examined in 28 patients before laparoscopic adrenalectomy; 17 patients with reduced BMD were then included in the longitudinal evaluation. BMD was determined using dual energy X-ray absorptiometry (DXA) before and at 3, 6, 12, 18, and 24 months after adrenalectomy. The prevalence of osteoporosis was 64% (95% confidence interval 44-81%). Preoperative BMD of the lumbar spine in the lateral projection was significantly lower than that of the femoral neck (mean+/-SD score: -3.53+/-0.75 vs. -1.54+/-0.22, p=0.003). A significant increase in BMD was observed at 3 months after surgery in the lumbar spine (p=0.0004). Improvement at both sites was maintained at 24 months after surgery. The postoperative percentage change in BMD of the lumbar spine was significantly higher than that of the femoral neck (mean+/-SD 36.7%+/-26.5% vs. 11.2%+/-12.1%, p=0.01). The change in the seven premenopausal patients was significantly higher than that in the three postmenopausal patients (p=0.0006). Surgical cure of hypercortisolism provides significant improvement in BMD in patients with Cushing's syndrome due to adrenal adenoma. The improvement is particularly apparent in the lumbar spine measured in the lateral projection. Premenopausal women are more likely to benefit from surgery in terms of secondary osteoporosis.

Denosumab: RANKL inhibition in the management of bone loss

Receptor activator of nuclear factor-kB (RANK), its ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) together play a key role in osteoclastogenesis. Alterations in the RANKL/ OPG ratio are central in the pathogenesis of bone loss, from osteoporosis in all its forms to malignancy-induced bone loss. This fact has led to the search for drugs capable of targeted RANKL inhibition in the management of skeletal disorders associated with bone loss. Promising preclinical data using OPG have paved the way for the development of the new agent denosumab, a high-affinity, high-specificity, fully human monoclonal antibody to RANKL, shown to be able to induce a dose-dependent, rapid, profound and sustained inhibition of bone resorption lasting for months after a single subcutaneous injection in healthy postmenopausal women, men and patients with multiple myeloma or metastatic breast cancer. Data from a phase II study in postmenopausal women with low bone mineral density (BMD) demonstrate that the sustained inhibition of bone resorption induced by three or six monthly subcutaneously administered denosumab was associated with significant increases in BMD for up to two years of treatment. Antifracture efficacy and long-term skeletal and extraskeletal safety of denosumab are being addressed in ongoing phase III trials. The potential of denosumab to prevent bone loss has also been demonstrated in malignancy-induced bone loss. Ongoing studies in rheumatoid arthritis are also promising.

Long-term 1,25(OH)2 vitamin D therapy increases bone mineral density in osteopenic women. Comparison with the effect of plain vitamin D

Although the bone protective effect of vitamin D has been studied intensively, the usefulness of 1,25(OH)2D3 in treating osteoporosis is still questionable. The aim of the present prospective study was to evaluate the effect of a standard pharmacological dose of 1,25(OH)2D3 in postmenopausal unsubstituted women. Our study group comprised 52 post-menopausal women with low normal or osteopenic values of bone mineral density (BMD). Thirty-two of them were treated with 1,25(OH)2D3 for 3 years. In parallel, another group of women was treated with cholecalciferol (n=20). Vitamin D adequacy before administration of 1,25(OH)2D3 and compliance with treatment were checked by serum PTH levels, which were assessed at the start and three times in the course of treatment. Increase in BMD at the spine at the end of the 1st, 2nd and 3rd years of treatment with 1,25(OH)2D3 (expressed as a percentage of the value before treatment) was higher, but did not significantly differ from the effect of plain vitamin D. A significant increase in BMD at the hip at the end of the 3rd (but not the 1st and 2nd) year of treatment with 1,25(OH)2D3 was found (p<0.05, compared with the effect of plain vitamin D). The protective effect of cholecalciferol was found only on spine but not hip BMD. The study supports the hypothesis that long-term administration of 1,25(OH)2D3 is effective in treating low bone mass in postmenopausal women.