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J D Ringe

Publications and source records attributed to J D Ringe.

At least 19 recordsLinked to original sources
PubMed2007

Superiority of a combined treatment of Alendronate and Alfacalcidol compared to the combination of Alendronate and plain vitamin D or Alfacalcidol alone in established postmenopausal or male osteoporosis (AAC-Trial).

A combined therapy with the strongly antiresorptive Alendronate and the pleiotropically acting D-hormone analogue Alfacalcidol may have additive effects on bone quality, falls and fracture risk in established osteoporosis. The aim of this study (Alfacalcidol Alendronate Combined-AAC) was to compare the efficacy and safety of a combined parallel therapy with Alendronate and Alfacalcidol to the treatment with either Alendronate in combination with plain vitamin D or Alfacalcidol alone in patients with established postmenopausal or male osteoporosis. Ninety patients were included as matched triplets to receive randomly either 1 microg Alfacalcidol daily + 500 mg calcium (group A, n = 30) or 70 mg Alendronate weekly + 1,000 mg calcium + 1,000 IU vitamin D daily (group B, n = 30) or 1 microg Alfacalcidol daily + 70 mg Alendronate weekly + 500 mg calcium daily (group C, n = 30). Patients were recruited in one centre and were followed up for 24 months. Analysis was intention-to-treat and the primary outcome was lumbar spine and total hip bone mineral density (measured observer blind). BMD was measured at the lumbar spine and at the proximal femur with dual energy X-ray absorptiometry (LUNAR Prodigy, GE, USA) at the beginning and after 12 and 24 months. During the 2-year-study we observed descriptively significant increases at the lumbar spine of 3.0% in group A compared to baseline, of 5.4% in group B and of 9.6% in group C, respectively. The superiority of the Alendronate + Alfacalcidol treatment group over Alfacalcidol alone and over Alendronate + vitamin D was of more than large rele-vance (both tests: MW > 0.71; CI-LB > 0.64; P < 0.001). We also observed median increases of the BMD at the total hip of 1.5% in group A, of 2.4% in group B and of 3.8% in group C, respectively. The superiority of group C over group A and over group B again was relevant and statistically significant in a descriptive sense. After 2 years there was a tendency towards higher rates of vertebral and non-vertebral fractures in group A and B as compared to C. Taking both fracture types together we observed 9, 10 and 2 "osteoporotic fractures" in groups A, B and C, respectively. The comparison of group C with pooled groups A and B and with each single group gave a relevantly lower fracture rate for the combination of Alendronate and Alfacalcidol. Furthermore a lower rate of falls was observed for the combination Alendronate plus Alfacalcidol versus Alendronate + vitamin D, but not versus Alfacalcidol alone. We found 80% of the patients in the Alendronate + Alfacalcidol group free from back pain at month 24, compared to 30% in the Alendronate + vitamin D and 43% in the Alfacalcidol monotherapy group. The superiority is relevant (both tests: MW > 0.64; CI-LB > 0.56; P < 0.003). Pain decrease also occurred more rapidly in the Alendronate + Alfacalcidol group than in the other groups. In general side effects in all groups were mild, and only four cases of moderate hypercalcuria in group A and one in group C were reported, but no case of hypercalcemia was documented. In conclusion, the combination therapy with Alendronate and Alfacalcidol exhibited superiority in terms of BMD, overall fractures, rate of falls and back pain over either Alendronate in combination with plain vitamin D or Alfacalcidol alone. The overall safety profiles of the three treatment regimens were found to be not different in this study.

Aged↗
PubMed2005

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.

Adult↗
PubMed2005

Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study.

Osteoporosis is prevalent in men with an estimated one in eight men older than 50 years suffering from osteoporotic fracture, and a higher mortality rate after fracture among men compared with women. There are few approved therapies for osteoporosis in men. This observational study assesses the efficacy and safety of risedronate in the treatment of men with primary and secondary osteoporosis. A single-center, open label, randomized, prospective 1-year study was conducted in men with primary or secondary osteoporosis. Patients were randomized to risedronate (risedronate 5 mg/day plus calcium 1,000 mg/day and vitamin D 800 IU/day) or control groups (alfacalcidol 1 mug/day plus calcium 500 mg/day or vitamin D 1,000 IU/day plus calcium 800 mg/day). Bone mineral density (BMD) measurements, X-rays of the spine, a medical history and physical exam, and patient self-assessments of back pain were performed at baseline and 12 months. Blinded semi-quantitative fracture assessment was conducted by a radiologist. A total of 316 men with osteoporosis were enrolled in the trial (risedronate, n=158; control, n=158). At 1 year lumbar spine BMD increased by 4.7% in the risedronate group versus an increase of 1.0% in the control group (P<0.001). Significant increases in BMD at the total hip and femoral neck were also observed with risedronate compared with the control group. The incidence of new vertebral fracture in the risedronate group was reduced by 60% versus the control group (P=0.028). Daily treatment with risedronate for 12 months significantly increased BMD at the lumbar spine, femoral neck and total hip and significantly reduced the incidence of new vertebral fractures. This is the first prospective, randomized, controlled trial to demonstrate a significant reduction in vertebral fractures in 1 year in men with primary or secondary osteoporosis.

Aged↗
PubMed2005

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.

Absorptiometry, Photon↗
PubMed2003

[Too many osteoporosis patients are undertreated with analgesics. Chronic pain promotes bone loss].

The leading subjective symptom of osteoporosis is severe or intolerable back pain. Resulting partial or complete immobilization increases the risk of muscular atrophy and bone loss, and thus the risk of fractures. Pain management in osteoporotic patients is either not applied at all, or only inadequately. When pain and immobility are pronounced, primary treatment with opioids and individually adapted co-analgesics is called for. Initial experience with opioid therapy in osteoporosis reveals rapid amelioration and improved mobility. Concern about addiction, development of tolerance and problems on discontinuation are unjustified.

Analgesics↗
PubMed2003

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.

Adjuvants, Immunologic↗
PubMed2003

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.

Adjuvants, Immunologic↗
PubMed2003

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.

Aged↗
PubMed2003

Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis.

OBJECTIVE: Corticosteroids are widely prescribed, although treatment-related side-effects are common. Of these adverse events (AEs), osteoporosis is considered the most serious. Currently, oral bisphosphonates are the standard treatment for corticosteroid-induced osteoporosis (CIO). However, intermittent intravenous (i.v.) therapy may have advantages, including lack of gastrointestinal AEs, improved bioavailability and increased compliance. This study investigated the efficacy and safety of 3-monthly i.v. ibandronate bolus injections in patients with established CIO. The results from a planned 2-yr interim analysis are reported. METHOD: In this controlled, prospective, open-label, parallel-group study, 104 patients (49 men and 55 women) with established CIO (mean T-score <-2.5 s.d. at the lumbar spine (L2-L4) received daily calcium (500 mg) plus either 3-monthly i.v. ibandronate (2 mg) bolus injections or oral daily alfacalcidol (1 micro g). The primary end-point was bone mineral density (BMD) change at the lumbar spine, femoral neck and calcaneus after 24 months. RESULTS: Compared with oral daily alfacalcidol, i.v. ibandronate produced significantly superior gains in mean (+/-s.d.) BMD at the lumbar spine (2.2+/-3.1 vs 11.9+/-7.4%; P<0.001), femoral neck (1.3+/-1.8 vs 4.7+/-4.0%; P<0.001) and calcaneus (7.6+/-3.8 vs 15.5+/-10.7%; P<0.0001) after 2 yr. Consistent with these BMD gains and, although the study was not powered for fractures, a trend towards a reduction in vertebral fractures and greater back pain relief was seen in the ibandronate group. The overall incidence of AEs was similar in the two treatment arms. CONCLUSIONS: Three-monthly i.v. ibandronate bolus injections are significantly superior to alfacalcidol in the treatment of CIO. These data confirm the potential of ibandronate for the treatment of osteoporosis associated with corticosteroid use. The ease of administration, lack of AEs and good compliance associated with intermittent i.v. ibandronate make it a potentially valuable alternative to oral bisphosphonate therapy for the treatment of CIO.

Aged↗
PubMed2002

Transdermal fentanyl for the treatment of back pain caused by vertebral osteoporosis.

Pain relief for patients with osteoporosis is important to maintain mobility and facilitate physical therapy. Transdermal fentanyl may be useful but has not been studied systematically. Patients with at least one osteoporotic vertebral fracture requiring strong opioids were enrolled and received transdermal fentanyl. Treatment history, pain, ease of physical therapy, and quality of life were recorded at baseline and after 4 weeks. Of 64 patients enrolled, 49 completed the study; 12 withdrew because of adverse events, most commonly nausea, vomiting, or dizziness. Pain at rest and on movement decreased significantly from baseline to final assessment (mean scores 7.84 and 8.55, respectively, at baseline, falling to 3.56 and 4.50 after 4 weeks). Quality of life improved significantly, and 61% of patients were satisfied with the treatment. Ability to undergo physical therapy improved significantly. Transdermal fentanyl is useful for the treatment of severe back pain caused by osteoporosis.

Administration, Cutaneous↗
PubMed2002

Treatment of male osteoporosis: recent advances with alendronate.

Overall, the data from the two alendronate studies clearly document the efficacy and safety of alendronate in osteoporotic men. The positive effects of alendronate on BMD, markers and fractures are very consistent between studies. Importantly, they are also very consistent with the results of multiple clinical studies conducted in postmenopausal women with osteoporosis. Treatment with 10 mg alendronate for 2 years produced significant and clinically meaningful increases in BMD, similar to those previously observed in postmenopausal women. Data from studies including men and women confirm the similarity of response suggested by single-gender studies. Consistent with much larger studies in postmenopausal women, alendronate 10 mg/day also reduced the incidence of new vertebral fracture and, correspondingly, reduced height loss. The safety and tolerability of alendronate in men was favorable and consistent with the safety profile previously observed in postmenopausal women. Alendronate represents an important and needed therapeutic advancement in the management of osteoporosis in men.

Adult↗
PubMed2001

[Fluorides and bisphosphonates in the treatment of osteoporosis].

The therapeutic aim in osteoporosis to maintain or increase bone mass can be achieved by inhibition of osteoclastic resorption (antiresorptive treatment), stimulation of osteoblastic formation (anabolic treatment), or a combination of both strategies. Antiresorptive therapy of osteoporosis with the nitrogen-containing bisphosphonates alendronate and risedronate is regarded today as evidence-based medicine. A significant reduction in the number of patients with new vertebral fractures has been documented already after 1 year. Anabolic therapy with fluoride was studied less extensively. The low price of fluoride salts and the lack of a patent protection may have contributed to this deficit in large studies. However, several recent medium-sized trials with a low-dose fluoride regimen consistently show a continuous increase in bone density and also a decrease in the rate of new fracture events. In our own pilot study with intermittent etidronate/fluoride therapy, we found significantly additive effects on bone mineral density. A larger trial with this therapeutic strategy using fractures as the primary endpoint would be of great interest.

Aged↗
PubMed2001

Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates.

Alendronate has been approved as a first antiresorptive drug for treatment of osteoporosis in men. Except for fluoride, in some countries so far there has been no approved anabolic substance for the treatment of male osteoporosis. From small studies in men and male patients included in studies on postmenopausal osteoporosis there is sufficient evidence that fluoride has the same osteoblast-stimulating potency in men and women. In our own study on 64 men with idiopathic osteoporosis without prevalent fractures, a low-dose intermittent fluoride regimen (15 mg fluoride ions 3 months on, 1 month off) resulted in an average gain of lumbar spine BMD of 3% per year and a lower rate of incident fractures as compared with patients treated with calcium only. A combination of fluoride with an antiresorptive drug may improve the therapeutic results in terms of pattern of biochemical marker response and gain in BMD. This was shown for postemopausal osteoporosis in several studies using fluoride and hormone replacement therapy (HRT). Encouraged by a Dutch study using etidronate/fluoride in corticoid-induced osteoporosis, we performed a pilot study in 33 men with severe established primary osteoporosis giving cyclically etidronate for 14 days followed by fluoride plus calcium/vitamin D for 76 days. This combined regimen resulted in significantly higher increases of BMD than fluoride or etidronate alone. In an ongoing trial we are studying a continuous, combined treatment of alendronate and fluoride plus calcium/vitamin D in established idiopathic osteoporosis in men. The results of a preliminary evaluation look very promising. A large study with a bisphosphonate plus fluoride, taking fractures as the primary endpoint and bone biopsies to assess safety, would be very valuable.

Alendronate↗