Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme-linked immunosorbent assay for measuring type I collagen degradation products in serum (S-ELISA) was developed. The assay uses a high affinity polyclonal antibody which reacts with an isomerized form of an 8 amino acid sequence of the C-telopeptides of type I collagen (EKAHD-beta-GGR). Cross-reactivity to a nonisomerized synthetic peptide form of the 8 amino acid sequence is less than 0.2%. Values obtained in a group of premenopausal women (age, 33.3 +/- 3.11 years) were 69 +/- 24 ng/ml(n = 22). In a group of early postmenopausal women (age, 51.8 +/- 1.88 years) values obtained were 125 +/- 43 ng/ml (n = 46), which represents an increase of 81% (p < 0.001). Values found in untreated patients with Paget's disease were 234 +/- 95 ng/ml (n = 15), and for primary hyperparathyroidism we found 335 +/- 82 ng/ml (n = 10). Intravenous administration of a bisphosphonate (Pamidronate) to Paget's disease patients for 3 days was reflected in the S-ELISA by a decrease in the values of 55% when compared with values before treatment (n = 15). Following treatment with another bisphosphonate (Alendronate) for 6 months, values were decreased to 48 +/- 19 ng/ml (n = 12), which corresponds to a 62% decrease. Clinical results presented in this context support that the assay is a sensitive and specific index of bone resorption. It may, therefore, prove useful in the follow up of treatment of patients with metabolic bone diseases and in the clinical investigation of osteoporosis.
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PMID:Measurement of bone degradation products in serum using antibodies reactive with an isomerized form of an 8 amino acid sequence of the C-telopeptide of type I collagen. 920 1

The majority of the patients with advanced prostate carcinoma have painful skeletal metastases, which are responsible for significant skeletal morbidity and disability. Most of these metastases are osteosclerotic, but it has been shown that the abnormal osteoblastic bone formation within metastases is preceded by osteoclastic activation, which appears to be associated with bone pain. This provides the rationale for using bisphosphonates, which are powerful and selective inhibitors of osteoclastic bone resorption. Several bisphosphonates have been shown to be clinically useful for the treatment of several conditions characterized by abnormal osteoclastic bone resorption, including Paget's disease, primary hyperparathyroidism, myelomatosis, and skeletal metastases. Its efficacy in relieving pain in patients with skeletal metastases due to prostate carcinoma has been confirmed in a few studies. The bisphosphonate clodronate was extensively investigated in the study unit. When infused intravenously i.v. (300 mg/day) relief of bone pain become appreciable within 3 days, sometimes preceded by a transient pain flare. These clinical results are very consistent and the residual pain usually is of extraosseous origin. Thus, with regard to pain of strictly bone origin, unresponsive patients are quite rare. Oral administration also is effective, but due to its limited intestinal absorption the effective dose is on the order of 1600-3200 mg/day. These doses usually are well tolerated, but they may be a problem for severely ill patients. Furthermore, the efficacy of treatment becomes apparent only after a few days. Thus, oral clodronate usually is adopted as a continuation of an i.v. course. The duration of the i.v. therapy should be individualized, but usually the more prolonged the treatment the longer the duration of the effect. For practical reasons, clodronate is infused daily for 5 days (Monday-Friday) and the treatment course is repeated at the time of any significant recurrence. The oral continuation prevents or delays the recurrence of bone pain in most patients, but in some patients this therapy has to be integrated occasionally with i.v. infusion. The duration of the effect for the same bioavailable dose is somewhat related to the degree of malignancy of the primary tumor. In an uncontrolled study, the author also evaluated the effectiveness of alendronate given either i.v. or orally. A single infusion of 5 mg alendronate i.v. produces roughly the symptomatic effect of 5 i.v. infusions of 300 mg clodronate. Alendronate, 40 mg orally/day, was effective in reducing bone pain in 11 of 12 patients with bone metastases due to prostate carcinoma but who were not confined to bed. In some patients with prostate carcinoma and a diffuse metastatic invasion of the skeleton, there is indirect biochemical and histologic evidence of osteomalacia. This can be aggravated by bisphosphonate administration because of the transient striking prevalence of osteoblastic activity over bone resorption, which also occasionally causes the appearance of symptomatic hypocalcemia. Therefore, the use of large oral supplements of calcium is recommended, particularly at the start of therapy. It is conceivable that these calcium supplements also may be able to improve the final clinical outcome of the bisphosphonate therapy. In conclusion, administration of large doses of bisphosphonates is one of the most cost-effective palliation treatments for patients with prostate carcinoma with bone metastases, both as first-line therapy and in the long term. With appropriate doses, a large proportion of patients can be maintained free of bone pain until death. Studies of the ability of lower doses to prevent skeletal morbidity in patients without metastases or with asymptomatic bone lesions are warranted.
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PMID:Bisphosphonates in prostate carcinoma. 936 35

We investigated the effect of alendronate on calcium, PTH, and bone mineral density in 27 female and 5 male patients with primary hyperparathyroidism. The treatment group [n = 14; T score < or = -2.5 SD at the femoral neck (FN) or T < or = -1.0 SD plus previous nonvertebral fracture] was given alendronate 10 mg/d for 24 months. The second group (n = 18; T score > -2.5 SD at the FN) was untreated. Biochemistry was repeated at 1.5, 3, 6, 12, 18, and 24 months, and dual-energy x-ray absorptiometry at 12 and 24 months. There were no significant between-group baseline differences in calcium, creatinine, or PTH. Alendronate-treated patients gained bone at all sites [lumbar spine (LS), 1 yr gain, +7.3 +/- 1.7%; P < 0.001; 2 yr, +7.3 +/- 3.1%; P = 0.04). Untreated patients gained bone at the LS over 2 yr (+4.0 +/- 1.8%; P = 0.03) but lost bone elsewhere. Calcium fell nonsignificantly in the alendronate group between baseline (2.84 +/- 0.12 mmol/liter) and 6 wk (2.76 +/- 0.09 mmol/liter), with a nonsignificant rise in PTH (baseline, 103.5 +/- 14.6 ng/liter; 6 wk, 116.7 +/- 15.6 ng/liter). By 3 months, values had reverted to baseline. In primary hyperparathyroidism, alendronate is well tolerated and significantly improves bone mineral density at the LS (with lesser gains at FN and radius), especially within the first year of treatment. Short-term changes in calcium and PTH resolve by 3 months.
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PMID:Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study. 1236 23

The effect of biphosphonate therapy on bone mineral density (BMD) in patients with primary hyperparathyroidism (PHP) is unknown. Forty postmenopausal women (mean age, 70 yr) with PHP were randomized to receive alendronate 10 mg/d or placebo for 48 wk, followed by treatment withdrawal for 24 wk. The mean (+/-SD) changes in BMD at femoral neck (+4.17 +/- 6.01% vs. -0.25 +/- 3.3%; P = 0.011) and lumbar spine (+3.79 +/- 4.04% vs. 0.19 +/- 2.80%; P = 0.016) were significantly higher with alendronate at 48 wk. Serum calcium was reduced with alendronate but not placebo (-0.09 vs. +0.01 mmol/liter; P = 0.018). Serum bone-specific alkaline phosphatase activity was lower with alendronate from 12 wk onward and increased 24 wk after treatment withdrawal (21.1 +/- 12.8 to 7.3 +/- 4.9 IU/liter at 48 wk, and 15.0 +/- 14.8 IU/liter 24 wk after withdrawal; P = 0.002 for trend). Osteocalcin concentration decreased at 48 wk and increased 24 wk after alendronate withdrawal (P = 0.019 for trend of change over time) but not with placebo. Urinary N-telopeptide/creatinine ratio decreased with alendronate at 48 wk and increased 24 wk after treatment withdrawal (P = 0.008 for trend). N-telopeptide/creatinine ratio did not change with placebo. Alendronate improves BMD and reduces bone turnover markers in postmenopausal women with PHP.
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PMID:Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism. 1257 84

The management of oestrogen deficiency bone loss needs to include general measures to protect against osteoporosis, the identification and treatment of other reversible causes of bone loss, and the use of proven agents for the treatment of osteoporosis. The general measures include improved physical activity, adequate diet (paying particular attention to calcium and vitamin D), and avoidance of behaviours that promote bone loss, such as smoking and alcohol abuse. The diseases that should be identified, other than estrogen-deficiency, include primary hyperparathyroidism, thyrotoxicosis and celiac disease. The treatments that are proven to prevent fractures in women with estrogen deficiency, include hormone replacement therapy, raloxifene, nasal calcitonin, bisphosphonates, (alendronate and risedronate) and parathyroid hormone. The most appropriate therapy in the younger woman is HRT, although the trial-based evidence that HRT prevents fractures is not strong. There is a wide choice of preparations and the use of continuous combined preparations avoids regular menstrual periods, one of the limitations to the use of HRT. Raloxifene has less effect on bone mineral density than HRT, but a similar effect on vertebral fractures and does not result in menstrual bleeding or increased risk of breast cancer. There is recent evidence suggesting that the beneficial effects on lipids translate into reduced risk of cardiovascular disease. Bisphosphonates are the standard treatment for the older woman with osteoporosis. Alendronate has been found to reduce the risk of spine, hip, and wrist fractures and has approval for a once weekly regimen, an approach that appears to prevent GI side effects. Risedronate reduces the risk of spine and non-vertebral fractures within the first year of treatment and has been shown to reduce the risk of hip fracture. It has not been associated with an excess of GI side effects. Parathyroid hormone therapy results in increases in BMD that are even greater than estrogen and the bisphosphonates and to an even greater reduction in the risk of fractures, particularly non-vertebral fractures. It works by stimulation of bone formation rather than by inhibition of bone resorption. However, it has to be given by daily injection. Thus, we have a wide choice of therapies for the woman with osteoporosis due to ovarian failure.
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PMID:Management of osteoporosis due to ovarian failure. 1286 23

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.
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PMID:Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial. 1524 Jun 9

Primary hyperparathyroidism (PHPT) is often associated with low bone mineral density (BMD). An open-labeled, prospective trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with advanced PHPT. All patients had symptomatic PHPT and met surgical guidelines however refused surgery. Nineteen patients was treated with alendronate for 2 years. The primary outcome index, BMD, was measured at the lumbar spine (LS) and femoral neck (FN) every 6 months by dual-energy x-ray absorptiometry. Serum calcium, phosphorous and PTH, and urinary calcium excretion were monitored every 3 months. Treatment with alendronate over 2 years was associated with a significant (5.3+/-0.4%; p<0.01) increase in LS BMD in comparison with baseline. FN BMD increased significantly at 24 months with alendronate by 2.5%+/-0.7 (p<0.01) from baseline. Serum calcium, phosphorus and PTH, and urine calcium excretion did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS and FN at 24 months from baseline values with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in symptomatic PHPT among those with low BMD, who are candidates for surgery but either decline or for whom surgery is contraindicated.
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PMID:[Alendronate increases bone mineral density in patients with symptomatic primary hyperparathyroidism]. 1682 Dec 4