To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab mo...To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group(18 cases) or a denosumab plus vitamin D supplementation group(combination group; 23 cases). We measured serum bone alkaline phosphatase(BAP), tartrate-resistant acid phosphatase(TRACP)-5 b and urinary N-terminal telopeptide of type-I collagen(NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density(BMD) of L1–4 lumbar vertebrae(L)-BMD and bilateral hips(H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5 b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months(except at 12 months for NTX). In the combination group, TRACP-5 b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months(P < 0.05).BAP was significantly suppressed in both groups at 2–12 months. L-BMD significantly increased at 8 and12 months(8.9%) in the combination group and at 4, 8 and 12 months(6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group(3.6%) compared with the denosumab group(1.2%) at 12 months(P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD(especially at the hips).展开更多
BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BM...BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.展开更多
This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. ...This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups:(1) denosumab group(denosumab alone, n=13); and(2) combination group(denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase(BAP), serum tartrate-resistant acid phosphatase(TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen(NTX), and bone mineral density(BMD) of L1–4 lumbar vertebrae(L-BMD)and bilateral total hips(H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months(P<0.05). L-BMD was significantly increased at most time points in both groups, with a significant difference between the combination group and denosumab group at 24 months(17.2% increase versus 9.6% increase; P<0.05). There was no significant difference in H-BMD between the two groups, although the levels tended to be higher in the combination group than in the denosumab group(9.5% increase versus 5.6% increase). These findings suggest that denosumab+teriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.展开更多
Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- b...Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- binds RANKL with high affinity and specificity and inhibits RANKL action. Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of- 1.8 to - 4.0 at the lumbar spine or- 1.8 to- 3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open- label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C- telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis.展开更多
Intrapelvic prosthetic migration prosthesis following hip arthroplasty can occur due to aseptic loosening, infection, injury and malposition of the cup with chronic instability. Revision surgery is the treatment optio...Intrapelvic prosthetic migration prosthesis following hip arthroplasty can occur due to aseptic loosening, infection, injury and malposition of the cup with chronic instability. Revision surgery is the treatment option, but is often complex, is high risk owing to the co-morbidities of the patient, has higher complications and sometimes even patients refuse for the surgery. Osteoclast mediated bone resorption at the prosthetic bone interface is the main pathophysiology process involved in aseptic loosening associated intrapelvic migration. RANK/RANKL (Receptor Activated Nuclear factor κB Ligand) is the primary pathway responsible for the periprosthetic osteolysis, therefore, we have offered Denosumab which binds to RANKL and inhibits osteoclasts mediated bone resorption, to our two patients with intrapelvic prosthetic migration who have refused for the revision surgery. Here, we report the outcome of these two cases of Intrapelvic prosthetic migration following a hip arthroplasty that was treated using subcutaneous injection of 120 mg denosumab monthly for 3 months. Both the cases had good functional outcomes and radiographs showed good consolidation of bone around the prosthesis. These cases suggest denosumab can be repurposed to arrest further intrapelvic prosthetic migration due to its anti-resorptive and bone forming action and can avoid the need for a complex revision surgery.展开更多
文摘To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group(18 cases) or a denosumab plus vitamin D supplementation group(combination group; 23 cases). We measured serum bone alkaline phosphatase(BAP), tartrate-resistant acid phosphatase(TRACP)-5 b and urinary N-terminal telopeptide of type-I collagen(NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density(BMD) of L1–4 lumbar vertebrae(L)-BMD and bilateral hips(H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5 b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months(except at 12 months for NTX). In the combination group, TRACP-5 b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months(P < 0.05).BAP was significantly suppressed in both groups at 2–12 months. L-BMD significantly increased at 8 and12 months(8.9%) in the combination group and at 4, 8 and 12 months(6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group(3.6%) compared with the denosumab group(1.2%) at 12 months(P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD(especially at the hips).
文摘BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.
文摘This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups:(1) denosumab group(denosumab alone, n=13); and(2) combination group(denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase(BAP), serum tartrate-resistant acid phosphatase(TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen(NTX), and bone mineral density(BMD) of L1–4 lumbar vertebrae(L-BMD)and bilateral total hips(H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months(P<0.05). L-BMD was significantly increased at most time points in both groups, with a significant difference between the combination group and denosumab group at 24 months(17.2% increase versus 9.6% increase; P<0.05). There was no significant difference in H-BMD between the two groups, although the levels tended to be higher in the combination group than in the denosumab group(9.5% increase versus 5.6% increase). These findings suggest that denosumab+teriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.
文摘Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- binds RANKL with high affinity and specificity and inhibits RANKL action. Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of- 1.8 to - 4.0 at the lumbar spine or- 1.8 to- 3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open- label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C- telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis.
文摘Intrapelvic prosthetic migration prosthesis following hip arthroplasty can occur due to aseptic loosening, infection, injury and malposition of the cup with chronic instability. Revision surgery is the treatment option, but is often complex, is high risk owing to the co-morbidities of the patient, has higher complications and sometimes even patients refuse for the surgery. Osteoclast mediated bone resorption at the prosthetic bone interface is the main pathophysiology process involved in aseptic loosening associated intrapelvic migration. RANK/RANKL (Receptor Activated Nuclear factor κB Ligand) is the primary pathway responsible for the periprosthetic osteolysis, therefore, we have offered Denosumab which binds to RANKL and inhibits osteoclasts mediated bone resorption, to our two patients with intrapelvic prosthetic migration who have refused for the revision surgery. Here, we report the outcome of these two cases of Intrapelvic prosthetic migration following a hip arthroplasty that was treated using subcutaneous injection of 120 mg denosumab monthly for 3 months. Both the cases had good functional outcomes and radiographs showed good consolidation of bone around the prosthesis. These cases suggest denosumab can be repurposed to arrest further intrapelvic prosthetic migration due to its anti-resorptive and bone forming action and can avoid the need for a complex revision surgery.
