Effective and rapid treatment of painful localized transient osteoporosis (bone marrow edema) with intravenous ibandronate.

Localized transient osteoporosis (LTO; bone marrow edema syndrome) is a rare disorder of generally unknown etiology that is characterized by acute onset of disabling bone pain. Treatment options are currently limited and largely ineffective. The locally increased bone turnover and low bone mineral density (BMD) typical of LTO indicate a potential role for bisphosphonate therapy. Ibandronate, a potent nitrogen-containing bisphosphonate, has proven efficacy in the management of postmenopausal osteoporosis and corticosteroid-induced osteoporosis when administered as a convenient intermittent intravenous (i.v.) injection with a between-dose interval of 2 or 3 months. In a study of 12 patients with LTO, ibandronate was administered as an initial 4-mg i.v. dose with a second, optional injection of 2 mg at 3 months. Daily calcium and vitamin D supplements were provided. Pain was measured at baseline and at 1, 2, 3, and 6 months using a visual analog scale (VAS) of 1-10, and BMD was measured at baseline and 6 months. I.v. ibandronate provided rapid and substantial pain relief. The mean (SD) VAS score decreased from 8.4 (1.3) at baseline to 0.5 (0.7) at 6 months, at which time seven patients had achieved complete pain relief. At 6 months, mean lumbar spine BMD had increased by 4.0% (range -0.8 to 7.7%) in the overall population. I.v. ibandronate injection affords advantages over currently available oral and i.v. bisphosphonates and thus offers a promising therapeutic advance in the treatment of LTO.

Efficacy of etidronate and sequential monofluorophosphate in severe postmenopausal osteoporosis: a pilot study.

In a three-year pilot study on 52 women with severe postmenopausal osteoporosis, treatment with etidronate followed by calcium and vitamin D (ECaD) was compared to etidronate followed by monofluorophosphate, calcium and vitamin D (EFCaD). BMD in lumbar spine, total hip and femoral neck increased significantly more with EFCaD than with ECaD. Pain-mobility score decreased significantly more with EFCaD than with ECaD (p=0.006). New vertebral fractures occurred in three patients under EFCaD (12%) and in nine under ECaD (35%), (p=0.048). Three patients under EFCaD (12%) and 15 under ECaD (58%) did not respond to therapy (p of difference=0.001). Mild or moderate adverse reactions were reported by 25 patients, with no significant difference between the two groups. The pilot study suggests that etidronate, sequentially followed by monofluorophosphate, could be a safe, effective and relatively inexpensive therapy in severe postmenopausal osteoporosis.

Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis.

Supplementation therapy with plain vitamin D plus calcium is in general regarded as effective prevention or first-step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to compare the therapeutic efficacy of the D-hormone analog alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid (GC) therapy were included as matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n=103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n=101). The two groups were well matched in terms of mean age, sex ratio, mean height and weight, daily dosage, and duration of GC therapy, and the percentages of the three underlying diseases included chronic obstructive pulmonary disease, rheumatoid arthritis, and polymyalgia rheumatica. The baseline mean bone mineral density (BMD) values at the lumbar spine for the two groups were -3.26 (alfacalcidol) and -3.25 (vitamin D(3)) and, at the femoral neck, -2.81 and -2.84, respectively (T scores). Rates of prevalent vertebral and nonvertebral fractures did not differ between groups. During the 3-year study, we observed a median percentage increase of BMD at the lumbar spine of 2.4% in group A and a loss of 0.8% in group B ( P<0.0001). There also was a larger median increase at the femoral neck in group A (1.2%) than in group B (0.8%) ( P<0.006). The 3-year rates of patients with at least one new vertebral fracture were 9.7% among those assigned to the alfacalcidol group and 24.8% in the vitamin D group (risk reduction 0.61, 95% CI 0.24-0.81, P=0.005). The 3-year rates of patients with at least one new nonvertebral fracture were 15% in the alfacalcidol group and 25% in the vitamin D group (risk reduction 0.41, 95% CI 0.06-0.68, P=0.081). The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D (risk reduction 0.52, 95% CI 0.25-0.71, P=0.001). In accordance with the observed fracture rates, the alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group ( P<0.0001). Generally, side effects in both groups were mild, and only three patients in the alfacalcidol group and two in the vitamin D group had moderate hypercalcemia. We conclude that alfacalcidol plus calcium is highly superior to plain vitamin D3 plus calcium in the treatment of established GIOP.

Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study.

Our trial was a 3-year, open-label, prospective, comparative, clinical study comparing the effects of oral alendronate (ALN), 10 mg daily, and alfacalcidol (AC), 1 microg daily, on bone mineral density (BMD), fracture events, height, back pain, safety and tolerability in 134 men with established primary osteoporosis. All men received 500 mg calcium daily. BMD was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (DXA). Spine radiographs were obtained at baseline and every 12 months thereafter, and were evaluated by a radiologist blinded to treatment assignment. At 3 years, AC-treated patients showed a significant mean increase of 3.5% in lumbar spine BMD, compared with a mean increase of 11.5% in men receiving ALN ( p<0.0001 between groups). The corresponding increases in femoral neck BMD were 2.3% and 5.8% for the AC and ALN groups, respectively ( p=0.0015 between groups). Over 3 years, new vertebral fractures occurred in 24.2% of the AC-treated patients and in 10.3% of the ALN-treated patients ( p=0.040). ALN-treated patients also had a significantly lower height loss. There were no between-group differences regarding nonvertebral fractures or changes in back pain. Both therapies were well tolerated, with a compliance rate >90%. We conclude that although AC has significant effects on BMD, ALN has greater effects on BMD and fracture efficacy.

Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study.

Despite its well-known benefits, chronic corticosteroid therapy causes osteoporotic fractures in approximately 30-50% of patients treated. To prevent the occurrence of these fractures, treatment with oral bisphosphonates is recommended. However, current oral bisphosphonates, which are given either daily or weekly, are associated with stringent, inconvenient dosing guidelines. Less frequent dosing may provide greater acceptability. The objective of this study was to investigate the efficacy and safety of ibandronate, a highly potent nitrogen-containing bisphosphonate, when given by intravenous (i.v.) injection every 3 months in men and women with established corticosteroid-induced osteoporosis (CIO; lumbar spine [L2-L4] bone mineral density [BMD] T-score < or =-2.5). A total of 115 participants were assigned to receive daily calcium supplements (500 mg) plus either ibandronate (2 mg) injections every 3 months or daily oral alfacalcidol (1 microg), for 3 years. Intermittent i.v. ibandronate injections produced significantly greater increases in mean BMD at the lumbar spine (13.3% versus 2.6%, respectively; p<0.001), and femoral neck (5.2% versus 1.9%, respectively; p<0.001) versus daily oral alfacalcidol, after 3 years, relative to baseline. This study was not statistically powered to show a difference between the groups with respect to fracture incidence. Nevertheless, after 36 months, the frequency of patients with new vertebral fractures was significantly lower in the patients receiving ibandronate relative to those taking alfacalcidol (8.6% versus 22.8%, respectively; p=0.043). This is the first time that significant vertebral fracture reduction has been demonstrated with an i.v. bisphosphonate in CIO. Patients treated with i.v. ibandronate injections also experienced less back pain (p<0.001) and less height loss (p=0.001) than those receiving oral alfacalcidol. Both regimens were well tolerated. In conclusion, intermittent i.v. ibandronate injections are efficacious, well-tolerated, and convenient, and promise to offer physicians an important therapeutic advance in the management of osteoporosis.

Alendronate treatment of established primary osteoporosis in men: results of a 2-year prospective study.

Men with osteoporosis have been neglected in the past, and only a few therapeutic trials have been performed in men. The bisphosphonate, alendronate, has been widely used for the treatment of postmenopausal osteoporosis. This prospective, open label, active controlled, randomized clinical study compared the effects of oral alendronate (10 mg daily) and alfacalcidol (1 microg daily) on bone mineral density (BMD), safety, and tolerability in 134 males with primary established osteoporosis. All men received supplemental calcium (500 mg daily). After 2 yr, alfacalcidol-treated patients showed a mean 2.8% increase in lumbar spine BMD (P < 0.01) compared with a mean increase of 10.1% in men receiving alendronate (P < 0.001). The corresponding changes in femoral neck BMD were +2.2% and +5.2% for the alfacalcidol and alendronate groups, respectively (P = 0.009). The incidence rates of patients with new vertebral fractures were 18.2% and 7.4% for the alfacalcidol and alendronate groups, respectively (P = 0.071). Both therapies were well tolerated. Thus, alendronate produced favorable effects on BMD consistent with the results from another study in male osteoporosis. The average increase rates were higher than with alfacalcidol. Alendronate may be superior to alfacalcidol in the treatment of men with established primary osteoporosis.

[Osteoporosis in the man: diagnosis and therapy]. / Osteoporose beim Mann: Diagnostik und Therapie.

The prevalence of osteoporosis in men has been underestimated in the past. Vertebral fractures were found in about 10% in men of age 50 and over 20 to 30% of all hip fractures in advanced age occur in men. Lower life expectancy of men but also differences in bone geometry and remodeling contribute to the lower rate of fractures in comparison to the female gender. In men with suspected osteoporosis a thorough history, physical and clinical examination is mandatory to exclude other localized or generalized osteopathies and to differentiate in primary and secondary osteoporosis. Only some small studies have been published so far on treatment of osteoporosis in men, i.e. therapeutic decisions are mainly based on existing results in postmenopausal osteoporosis. The basis of treatment is calcium and vitamin D supplementation and individually adapted recommendations on life style and risk factor avoidance. In established osteoporosis in adequate analgesic therapy is very important. In cases with secondary osteoporosis, if possible, etiological therapy should be started. Antiresorptive therapy (e.g. calcitonin, bisphosphonates) or osteoanabolic therapy (e.g. fluoride) can later be added, while in idiopathic osteoporosis this is the first option. According to the existing experiences there is in general a good chance to ameliorate the condition in men. There is however an urgent need for further data on therapy of osteoporosis in men.

Avoidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate.

There are currently no trial-based recommendations for the treatment of idiopathic osteoporosis in men. A prospective, controlled, randomized 3-year study was conducted to evaluate the effects of intermittent, low-dose fluoride combined with continuous calcium supplementation on bone mass and future fracture events in men with this disease. Sixty-four men with idiopathic osteoporosis (mean age 53 years; mean T-score at L2-4, -2.75) and no previous vertebral fractures were randomly assigned to two treatment groups. Group A received intermittent (3 months on, 1 month off) treatment with monofluorophosphate 114 mg/day (i.e. 15 mg fluoride ions) plus continuous calcium supplementation (950-1000 mg/day). Group B received continuous calcium (1000 mg/day) alone. Bone mineral density was measured at the lumbar spine, hip and radius at 6-months intervals; thoracic and lumbar spine radiographs were obtained every 12 months. In group A bone density increased at all sites (by between +1.2% and +8.8%), while group B showed moderate decreases (by between -1.4% and -5.2%). After 36 months, bone densities at all sites in group A were significantly higher than those of group B. Three patients (10%) in group A suffered a total of 4 vertebral fractures versus 12 patients (40%) with 17 fractures in group B (p = 0.008). Non-vertebral fractures occurred in 3 patients in group A versus 11 in group B, though this difference was not significant. Back pain was significantly reduced in group A and unchanged in group B (after 3 years p = 0.0003). All side-effects were mild and transient. Early treatment of idiopathic osteoporosis in the male using the fluoride-calcium regimen we tested can improve cancellous and cortical bone density, reduce the incidence of vertebral fractures and attenuate back pain.

[Severe osteomalacia in endemic sprue. An important differential diagnosis in osteoporosis]. / Schwere Osteomalazie bei einheimischer Sprue. Eine wichtige Differentialdiagnose bei V. a. Osteoporose.

A 67-year-old woman has a 20-year history of recurrent abdominal pain, diarrhea and diffuse bone pain. During the course of numerous hospitalisations the diagnoses "iron deficiency anemia", "iron absorption disorder", "osteoporosis" and "hyperparathyroidism" had been made. Despite treatment with vitamin D3, calcium, fluorides and iron, the patient's condition deteriorated to such a degree that she became in need of constant care. After 20 years of illness, nontropical sprue (celiac disease) with secondary intestinal osteopathy was identified. High-dose parenteral treatment with vitamin D3, oral calcium supplementation and a gluten-free diet resulted in an improvement of the patient's condition within three months, and the patient can now largely look after herself again.