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Biomedical subjects

Nancy E Lane

Publications and source records attributed to Nancy E Lane.

At least 19 recordsLinked to original sources
PubMed2006

Sequential treatment of ovariectomized mice with bFGF and risedronate restored trabecular bone microarchitecture and mineralization.

Basic fibroblast growth factor (bFGF), a potent mitogen, has been found to restore trabecular bone mass and connectivity in osteopenic rats. The purpose of this study was to determine how sequential treatment of ovariectomized (OVXed) mice with bFGF followed by risedronate would restore trabecular microarchitecture and improve bone strength through alterations in bone mineralization. Six-month old female Swiss-Webster mice were OVXed or sham-operated and left untreated for 4 weeks to develop osteopenia. At week 5, a group of Sham and OVXed mice were treated with vehicle, and 3 other groups of OVXed mice were treated with bFGF (1 mg/kg daily, s.c., 5x/week) for 3 weeks. At week 8, one group of bFGF-treated mice was sacrificed and the other two bFGF-treated groups were treated with vehicle or risedronate (Ris, 5 microg/kg, s.c., 3x/week) for an additional 6 weeks. Study endpoints included trabecular microarchitecture by microCT, histomorphometry, bone turnover, degree of bone mineralization (DBM), and whole bone strength for the lumbar vertebral body. Compared to sham-operated animals, OVXed mice had significant reductions in trabecular bone volume, connectivity density, DBM, and bone biomechanical properties (P < 0.05). Treatment with bFGF resulted in higher trabecular bone structure and bone strength compared to pre-treatment sham control (P < 0.05). Treatment of OVXed mice with bFGF for 3 weeks followed by 6 weeks Ris maintained the trabecular microarchitecture gained by bFGF treatment, and DBM and bone strength were restored to baseline control levels. Also compared to Sham-operated animals, serum TGF-beta1 was transiently increased after OVX, increased an additional 100% after bFGF withdrawal, and decreased by 30% with risedronate. In addition, DBM was the strongest predictor for bone biomechanical properties (R2 > 0.7, P < 0.001). Serum TGF-beta1 correlated with bone turnover (DPD/Cr, osteocalcin) and was negatively correlated to DBM. Thus, in osteopenic mice, sequential treatment with bFGF followed by risedronate increased trabecular bone microarchitecture, DBM, and bone strength. In addition, suppression of the serum TGF-beta1 with risedronate was associated with increased DBM. Therefore, sequential treatment with bFGF and Ris restores trabecular architecture and allows mineralization of bone to increase, which appears to be beneficial to bone strength.

Animals↗
PubMed2006

Thiazolidinedione use and bone loss in older diabetic adults.

CONTEXT: Activation of peroxisome proliferator-activated receptor-gamma by thiazolidinediones (TZDs) results in lower bone mass in mice. OBJECTIVE: The objective of the study was to determine whether TZD use is associated with changes in bone mineral density (BMD) in older adults with type 2 diabetes. DESIGN: We analyzed 4-yr follow-up data from the Health, Aging, and Body Composition observational study. SETTING: The study was conducted in a general community. PATIENTS: White and black, physically able men and women, aged 70-79 yr at baseline with diabetes defined by self-report, use of hypoglycemic medication, elevated fasting glucose (>/=126 mg/dl), or elevated 2-h glucose tolerance test (>/=200 mg/dl) participated in the study. MAIN OUTCOME MEASURES: Whole-body, lumbar spine (derived from whole body), and hip BMD were measured by dual-energy x-ray absorptiometry at 2-yr intervals. RESULTS: Of 666 diabetic participants, 69 reported TZD use at an annual visit, including troglitazone (n = 22), pioglitazone (n = 30), and/or rosiglitazone (n = 31). Those with TZD use had higher baseline hemoglobin A(1c) and less weight loss over 4 yr but similar baseline BMD and weight than others with diabetes. In repeated-measures models adjusted for potential confounders associated with TZD use and BMD, each year of TZD use was associated with greater bone loss at the whole body [additional loss of -0.61% per year; 95% confidence interval (CI) -1.02, -0.21% per year], lumbar spine (-1.23% per year; 95% CI -2.06, -0.40% per year), and trochanter (-0.65% per year; 95% CI -1.18, -0.12% per year) in women, but not men, with diabetes. CONCLUSION: These observational results suggest that TZDs may cause bone loss in older women. These results need to be tested in a randomized trial.

Absorptiometry, Photon↗
PubMed2006

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.

BACKGROUND: Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. METHODS: We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. RESULTS: The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups. CONCLUSIONS: Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Epidemiology, etiology, and diagnosis of osteoporosis.

Osteoporosis, a major public health problem, is becoming increasingly prevalent with the aging of the world population. Osteoporosis is a skeletal disorder characterized by compromised bone strength, which predisposes the individual to an increased risk of fractures of the hip, spine, and other skeletal sites. The clinical consequences and economic burden of this disease call for measures to assess individuals who are at high risk to allow for appropriate intervention. Many risk factors are associated with osteoporotic fracture, including low peak bone mass, hormonal factors, the use of certain drugs (eg, glucocorticoids), cigarette smoking, low physical activity, low intake of calcium and vitamin D, race, small body size, and a personal or a family history of fracture. All of these factors should be taken into account when assessing the risk of fracture and determining whether further treatment is required. Because osteoporotic fracture risk is higher in older women than in older men, all postmenopausal women should be evaluated for signs of osteoporosis during routine physical examinations. Radiologic laboratory assessments of bone mineral density generally should be reserved for patients at highest risk, including all women over the age of 65, younger postmenopausal women with risk factors, and all postmenopausal women with a history of fractures. The evaluation of biochemical markers of bone turnover has been useful in clinical research. However, the predictive factor of these measurements is not defined clearly, and these findings should not be used as a replacement for bone density testing. Together, clinical assessment of osteoporotic risk factors and objective measures of bone mineral density can help to identify patients who will benefit from intervention and, thus, can potentially reduce the morbidity and mortality associated with osteoporosis-associated fractures in this population.

Absorptiometry, Photon↗
PubMed2006

Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus.

Survival of patients with systemic lupus erythematosus (SLE) has improved over the past decade, thanks to improved treatment of the disease, which now results in fewer fatal complications. This improvement has allowed physicians to focus their attention on the prevention of organ damage caused by this chronic, inflammatory disease, and by the medications used to control the disease. Osteoporosis is common in SLE patients; risk factors for osteoporosis include prolonged use of glucocorticoids, cyclophosphamide and possibly gonadotropin-releasing-hormone agonists. In premenopausal women with SLE, inflammation or SLE-related medications can increase bone turnover, which eventually weakens bone architecture, then reduces bone strength and increases the risk of fracture. Prevention and treatment of osteoporosis in SLE patients should entail a multifaceted approach. Levels of calcium, vitamin D and homocysteine should be evaluated, and age-appropriate supplementation instituted. The bone loss that results from systemic inflammation should be treated by reduction of the inflammation with glucocorticoids, potent anti-inflammatory agents or antiresorptive agents. The efficacy of this therapy can be monitored using bone mineral density scans. This Review briefly discusses the pathophysiology of the localized and generalized osteoporosis and osteonecrosis in SLE patients and recommends therapies to both prevent and treat these unfortunate complications of this disease.

Female↗
PubMed2005

Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice.

UNLABELLED: This study compares changes in bone microstructure in 6-month-old male GC-treated and female ovariectomized mice to their respective controls. In addition to a reduction in trabecular bone volume, GC treatment reduced bone mineral and elastic modulus of bone adjacent to osteocytes that was not observed in control mice nor estrogen-deficient mice. These microstructural changes in combination with the macrostructural changes could amplify the bone fragility in this metabolic bone disease. INTRODUCTION: Patients with glucocorticoid (GC)-induced secondary osteoporosis tend to fracture at higher bone mineral densities than patients with postmenopausal osteoporosis. This suggests that GCs may alter bone material properties in addition to BMD and bone macrostructure. MATERIALS AND METHODS: Changes in trabecular bone structure, elastic modulus, and mineral to matrix ratio of the fifth lumbar vertebrae was assessed in prednisolone-treated mice and placebo-treated controls for comparison with estrogen-deficient mice and sham-operated controls. Compression testing of the third lumbar vertebrae was performed to assess whole bone strength. RESULTS: Significant reductions in trabecular bone volume and whole bone strength occurred in both prednisolone-treated and estrogen-deficient mice compared with controls after 21 days (p < 0.05). The average elastic modulus over the entire surface of each trabecula was similar in all the experimental groups. However, localized changes within the trabeculae in areas surrounding the osteocyte lacunae were observed only in the prednisolone-treated mice. The size of the osteocyte lacunae was increased, reduced elastic modulus around the lacunae was observed, and a "halo" of hypomineralized bone surrounding the lacunae was observed. This was associated with reduced (nearly 40%) mineral to matrix ratio determined by Raman microspectroscopy. These localized changes in elastic modulus and bone mineral to matrix ratio were not observed in the other three experimental groups. CONCLUSIONS: Based on these results, it seems that GCs may have direct effects on osteocytes, resulting in a modification of their microenvironment. These changes, including an enlargement of their lacunar space and the generation of a surrounding sphere of hypomineralized bone, seem to produce highly localized changes in bone material properties that may influence fracture risk.

Animals↗
PubMed2005

Changes in serum fibroblast growth factor 2 in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34).

Since the ability of parathyroid hormone (PTH) to increase osteoblast maturation and activity is associated with basic fibroblast growth factor (bFGF) we determined the changes in serum bFGF levels in patients treated with human parathyroid hormone (hPTH) (1-34) for 12 months and 12 months follow up. All studied subjects (n=51) had postmenopausal osteoporosis, had been receiving long-term treatment with glucocorticoid plus estrogen or estrogen/progesterone and were randomly allocated either to a group receiving hPTH, 400 U/day (n=28), or to a control group (n=23). Osteocalcin (OST), bone-specific alkaline phosphatase (BSAP) and bFGF were monitored at the baseline, every 3 months for 18 months, and at 24 months. In the hPTH group, OST increased by more than 150% above baseline at 3 months and was maintained at this level throughout the treatment period. BSAP had increased more than 80% over the baseline level at 3 months and was maintained at 90% above baseline for the next 9 months. bFGF levels had increased by 45% at 3 months, 60% at 6 to 9 months (P<0.05) and had increased more than 90% from baseline by 12 months (P<0.05). We found that daily hPTH injections increased bFGF levels. These results support the hypothesis that up-regulation of bFGF could play a role in the osteoblastic response to PTH.

Administration, Cutaneous↗
PubMed2005

Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats.

Recently, basic fibroblast growth factor (bFGF) has been found to increase trabecular bone mass and connectivity in the proximal tibial metaphyses (PTM) in osteopenic rats. The purpose of this study was to determine the bone anabolic effects of bFGF in the lumbar vertebral body (LVB), a less loaded skeletal site with a lower rate of bone turnover than the PTM. Six-month old female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and untreated for 8 weeks to induce osteopenia. Then group 1 (sham) and group 2 (OVX) were treated subcutaneously (s.c.) with vehicle, and OVXed groups 3 and 4 were treated s.c. with PTH [hPTH (1-34) at 40 microg/kg, 5x/week] and bFGF (1 mg/kg, 5x/week), respectively, for 8 weeks. At sacrifice, the fifth LVB was removed, subjected to micro-CT for determination of trabecular bone structure and then processed for histomorphometry to assess bone turnover. The sixth LVB was used for mechanical compression testing (MTS, Bionix 858). The data were analyzed with the Kruskal-Wallis test followed by post-hoc testing as needed. After 16 weeks of estrogen deficiency, there were significant reductions in vertebral trabecular bone volume and trabecular thickness. Treatment with either bFGF or hPTH (1-34) increased BV/TV in OVX animals. Human PTH (1-34)-treated animals had significant increases in trabecular (48%) and cortical thickness (30%) and bone strength [maximum load (53%) and work to failure (175%)] compared to OVX + Vehicle animals. Treatment of osteopenic rats with bFGF increased bone volume (15%), trabecular thickness (13%), maximum load (45%) and work to failure (140%) compared to OVX + Vehicle animals (all P <0.05). Basic FGF increased trabecular bone volume in the lumbar vertebral body of osteopenic rats by restoring trabecular number, thickness and connectivity density. Also, bFGF improved bone mechanical properties (maximum force and work to failure) compared to the OVX + Vehicle group. Therefore, increasing the number, thickness and connections of the trabeculae contributes to increased bone strength in this small animal model of osteoporosis.

Animals↗
PubMed2005

Performance incentives in the Massachusetts behavioral health program.

Since 1996, the Massachusetts Behavioral Health Partnership (the Partnership/MBHP) has been the behavioral health carve-out vendor for the Commonwealth of Massachusetts Primary Care Clinician (PCC) Plan. Its use of performance standards and incentives has become one of the central organizing activities for both the Commonwealth and the vendor, and one of the program's hallmarks. Each year, the Commonwealth uses a participative process for generating suggestions for performance incentives, which are then negotiated with the Partnership. Success or failure of projects is judged in accordance with objective measures developed for each incentive project. From 1996 to 2004, 123 performance projects have been completed. Some projects have become contract requirements, and others have developed into programs or services. The performance incentive process blends features of more traditional performance standards with performance-based contracting approaches. This process gives both the Commonwealth and the Partnership the flexibility to reflect changing state policies and to develop a contract that meets the most current needs of members.

Massachusetts↗
PubMed2005

The management of secondary osteoporosis.

Secondary osteoporosis is common among patients being evaluated for osteoporosis. All men and premenopausal women with unexplained bone loss or a history of a fragility fracture should undergo a work-up for secondary osteoporosis. Also, postmenopausal women with risk factors for secondary osteoporosis should be carefully evaluated. The evaluation should include a thorough history, physical examination, bone mineral density testing, and laboratory testing. While there is no consensus for a cost-effective laboratory evaluation, some recommendations include: 25-hydroxyvitamin D, parathyroid hormone (PTH), serum and urine calcium, phosphate, creatinine, liver function tests, a complete blood count, testosterone in men, and thyroid-stimulating hormone. After a thorough review of the evaluation for secondary osteoporosis, this chapter reviews the pathophysiology and treatment of secondary osteoporotic disorders, including vitamin D insufficiency, osteomalacia, the osteoporosis of erosive inflammatory arthritis, ankylosing spondylitis, systemic lupus erythematosus, and osteoporosis related to anti-androgenic therapy for prostate cancer and aromatase inhibitor therapy for breast cancer. Physicians have a significant responsibility to evaluate and treat the underlying medical problem that is the cause of secondary osteoporosis and to optimize bone health in the individual patient.

Androgen Antagonists↗
PubMed2005

Association of statin use and development and progression of hip osteoarthritis in elderly women.

OBJECTIVE: . To examine the association between use of HMG CoA reductase inhibitor (statin) and development and progression of radiographic findings of hip osteoarthritis (OA) in elderly women. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained, a mean of 8 years apart, in 5674 women (69% of the total survivors) age 65 years and older from the Study of Osteoporotic Fractures. Hips were scored for individual radiographic features (IRF) and assigned a summary grade of radiographic hip osteoarthritis (RHOA) based on the number and type of IRF present. Statin use was recorded from prescription labels provided by participants at Year 6 and Year 8 of followup. We estimated odds ratios for the development of RHOA in hips without disease at baseline and for progression of RHOA in hips with baseline disease, using generalized estimating equations to account for correlations of right and left hips. RESULTS: RHOA was present in 936 hips of 745 women at baseline and there were 9318 hips without baseline RHOA. Overall, 7% of women in this cohort were statin users. Statin use was associated with increased odds of developing incident summary grade > or = 3 RHOA (OR 1.92, 95% CI 1.03-4.43, p = 0.045), but was not significantly related to other measures of new RHOA. In hips with baseline RHOA there was a consistent but nonsignificant trend toward decreased progression of RHOA in statin users (all OR between 0.69 and 0.76, with 95% CI between 0.29 and 1.67). CONCLUSION: Statin use may be associated with an increased risk of developing incident RHOA but does not adversely influence progression of established disease.

Aged↗
PubMed2004

Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity.

UNLABELLED: This investigation used capsaicin to selectively lesion unmyelinated sensory neurons in rats. Neuronal lesioning induced a loss of trabecular integrity, reduced bone mass and strength, and depleted neuropeptides in nerve and bone. These data suggest that capsaicin-sensitive sensory nerves contribute to trabecular bone integrity. INTRODUCTION: Familial dysautomia is an autosomal recessive disease in which patients suffer from unmyelinated sensory neuron loss, reduced BMD, and frequent fractures. It has been proposed that the loss of neurotransmitters synthesized by unmyelinated neurons adversely affects bone integrity in this hereditary syndrome. The purpose of this study was to determine whether small sensory neurons are required for the maintenance of bone integrity in rats. MATERIALS AND METHODS: Ten-month-old male Sprague-Dawley rats were treated with either capsaicin or vehicle. In vivo DXA scanning and micro CT scanning, and histomorphometry were used to evaluate BMD, structure, and cellular activity. Bone strength was measured in distal femoral sections. Body weight and gastrocnemius/soleus weights were measured and spontaneous locomotor activity was monitored. Peroneal nerve morphometry was evaluated using light and electron microscopy. Substance P and calcitonin gene-related peptide (CGRP) content in the sciatic nerve and proximal tibia were determined by enzyme immunoassay (EIA). Substance P signaling was measured using a sciatic nerve stimulation extravasation assay. RESULTS: Four weeks after capsaicin treatment, there was a loss of BMD in the metaphyses of the tibia and femur. In the proximal tibia, the osteoclast number and surface increased, osteoblast activity and bone formation were impaired, and trabecular bone volume and connectivity were diminished. There was also a loss of bone strength in the distal femur. No changes occurred in body weight, 24-h grid-crossing activity, weight bearing, or muscle mass after capsaicin treatment, indicating that skeletal unloading did not contribute to the loss of bone integrity. Capsaicin treatment destroyed 57% of the unmyelinated sensory axons, reduced the substance P and CGRP content in the sciatic nerve and proximal tibia, and inhibited neurogenic extravasation. CONCLUSION: These results support the hypothesis that capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. Capsaicin-sensitive neurons have efferent functions in the tissues they innervate, effects mediated by transmitters released from the peripheral nerve terminals. We postulate that the deleterious effects of capsaicin treatment on trabecular bone are mediated by reductions in local neurotransmitter content and release.

Absorptiometry, Photon↗
PubMed2004

Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state.

UNLABELLED: Integrin alphavbeta5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as alphavbeta3. Three-month-old beta5(-/-) female OVX mice had increased osteoclastogenesis ex vivo, and microCT assessment of trabecular bone volume was 53% lower than WT-OVX animals. These preliminary data suggest alphavbeta5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation. INTRODUCTION: Osteoclasts are unique resorptive skeletal cells, capable of degrading bone on contact to the juxtaposed matrix. Integrin alphavbeta5 is expressed on osteoclast precursors, structurally similar to alphavbeta3, and capable of recognizing the same amino acid motif. Given the structural relationship and reciprocal regulation of alphavbeta3 and alphavbeta5, the purpose of this study was to evaluate how alphavbeta5 might contribute to osteoclast maturation and activity. MATERIALS AND METHODS: Three-month-old wildtype (WT) and beta5(-/-) female mice had ovariectomy (OVX) or sham operations. The osteoclastogenic capacity of marrow-derived precursors, the kinetic, the circulating, and structural parameters of bone remodeling, was determined after 6 weeks of paired feeding. RESULTS AND CONCLUSIONS: OVX increased osteoclastogenesis ex vivo and in vivo. Osteoclast formation and prolonged pre-osteoclast survival were substantially enhanced in cultures containing beta5(-/-) cells whether obtained from sham-operated or OVX mice. Expression of cathepsin K, beta3 integrin subunit, and calcitonin receptor were accelerated in cultured beta5(-/-)osteoclasts. beta5(-/-) osteoclasts from OVX animals showed a 3-fold enhancement of net resorptive activity, with quantitative muCT showing trabecular bone volume loss after OVX 53% greater in beta5(-/-) OVX compared with similarly treated WT OVX mice (p < 0.05). alpha5beta3 seems to be an inhibitor of osteoclast formation, in contrast to alphavbeta3. In addition, loss of alphavbeta5 seems to accelerate osteoclast formation in the OVX model. Further examination of alphavbeta5 signaling pathways may enhance our understanding of the activation of bone resorption.

Animals↗
PubMed2004

Differences in hip quantitative computed tomography (QCT) measurements of bone mineral density and bone strength between glucocorticoid-treated and glucocorticoid-naive postmenopausal women.

UNLABELLED: Chronic treatment with glucocorticoids (GCs) leads to significant bone loss and increased risk of fractures. In chronically GC-treated patients, hip fracture risk is nearly 50%. The purpose of this investigation was to determine if there are differences in the quantities of trabecular and cortical bone and bone strength of the hip between GC-treated osteoporotic patients and controls. METHODS: Study subjects were GC-treated osteoporotic postmenopausal women, and controls were postmenopausal women, recruited for separate clinical trials. Quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) of the hip were obtained from all subjects. QCT outcome variables measured included total, cortical, and trabecular BMD of hip subregions (femoral neck and trochanter) and total hip. In addition, finite element modeling (FEM) was performed on a subset of 19 cases and 38 controls, matched on age (+/- 5 years), weight (+/- 5 kg), and history of hormone replacement (> 1 year use) to assess failure load in stance and fall loading conditions. Generalized linear models were used to adjust the QCT variables for covariates between groups. Multiple regression was performed to identify independent predictors of bone strength from the QCT variables. RESULTS: Compared with controls, GC-treated subjects were significantly (p < 0.05) younger, weighed less, and had more years of hormone replacement. QCT of the hip in GC-treated subjects for total femoral integral, cortical, and trabecular BMD averaged 4.9-23.2% (p < 0.002) less than controls, and similar results were seen by hip subregion including the trochanter and femoral neck. DXA of the total hip was 17% lower in GC subjects than controls (p < 0.05). Compared with controls, FEM failure load in GC subjects was 15% (p<0.05) and 16% (p = 0.07) lower for stance and fall loading conditions, respectively. Multiple regression analysis demonstrated that a combination of QCT measures was correlated with bone strength as measured by FEM. CONCLUSIONS: Chronic GC treatment in postmenopausal women resulted in significantly decreased BMD of the hip, measured by QCT, with loss of both trabecular and cortical bone. In addition, GC treatment decreased bone strength as determined by FEM. The reduced cortical and trabecular bone mass in the hip may contribute to the disproportionately high hip fracture rates observed in GC-treated subjects.

Absorptiometry, Photon↗
PubMed2004

Progression of radiographic hip osteoarthritis over eight years in a community sample of elderly white women.

OBJECTIVE: To describe progression over 8 years in a community-based sample of elderly women with radiographic findings of hip osteoarthritis (RHOA) with or without hip pain. METHODS: Baseline and followup anteroposterior pelvic radiographs were obtained at a mean +/- SD 8.3 +/- 0.4 years of followup in women age > or =65 years at the baseline examination of the Study of Osteoporotic Fractures. We evaluated progression in 936 hips of 745 women with one or more baseline findings of RHOA: summary OA grade > or =2, minimum joint space (MJS) < or =1.5 mm, definite femoral or acetabular osteophytes, definite superolateral joint space narrowing (JSN), or moderate or worse superomedial JSN. We separately examined progression in hips with an MJS between 1.5 mm and 2.5 mm. Hip pain and lower extremity disability were assessed by questionnaire and examination. Measures of progression included an increase in summary grade of radiographic findings, increase in total osteophyte score, decrease in MJS of > or =0.5 mm, total hip replacement (THR), and increase in lower extremity disability score. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for baseline radiographic predictors of progression were estimated using general estimating equations. RESULTS: During followup, 12.9% of women with baseline RHOA underwent THR, and 22.8% had substantial worsening of lower extremity disability, while 64.6% of hips with RHOA showed radiographic progression or were replaced. Progression was greater by all measures in the 37% of hips and 47% of women with both RHOA and hip pain at baseline. Of hips with pain, 23.6% progressed to THR compared with 2.7% of hips without pain (OR 8.1 [95% CI 4.2, 15.4], P < 0.001), and MJS decreased > or =0.5 mm in 53.7% of hips with pain compared with 30.7% of hips without pain (OR 1.9 [95% CI 1.4, 2.6], P < 0.001). Women with hip pain were more likely to have worsened lower extremity disability (29.3% versus 17.6%; OR 1.8 [95% CI 1.2, 2.8], P = 0.0053). Hips with an MJS >1.5 mm and < or =2.5 mm (n = 1,868) had primarily superomedial narrowing and comparatively low rates of progression that did not differ by hip pain. Femoral osteophytes, superolateral JSN, and subchondral bone changes were independent predictors of progression. CONCLUSION: Among women recruited from the community, radiographic and clinical progression was greater in those with symptomatic RHOA, but still substantially less frequent than previously reported for hip OA patients in clinical settings. Asymptomatic RHOA and hips with an isolated finding of mild JSN (MJS of 1.5 mm to 2.5 mm) were unlikely to progress over 8 years.

Aged↗
PubMed2004

Parathyroid hormone: evolving therapeutic concepts.

PURPOSE OF REVIEW: Osteoporosis results from a loss of bone mass and structure such that bones break with very little trauma. To reduce bone loss and improve strength, antiresorptive agents have been instituted. Just more than a year ago, a 34-amino acid fragment of parathyroid hormone (recombinant human parathyroid hormone 1-34) was approved for the treatment of osteoporosis. The parathyroid hormone treatment works by stimulating bone formation on all bone surfaces and is referred to as an osteoanabolic agent. The purpose of this article is to review initial phase 2 and phase 3 studies that establish the effectiveness of this agent to treat osteoporosis. RECENT FINDINGS: In addition, studies that use parathyroid hormone in combination with antiresorptive agents and sequentially are reviewed. Last, unresolved issues related to the duration of use of parathyroid hormone are discussed. SUMMARY: In summary, parathyroid hormone compounds are a major advance in the treatment of osteoporosis. Additional research will enlighten clinicians on the most efficacious way to use them.

Clinical Trials as Topic↗
PubMed2004

Changes in serum receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34).

Changes in biochemical markers of bone turnover following intermittent injections of human (h)PTH (1-34) suggest that bone formation is initially favored over bone resorption. hPTH (1-34) is also known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines, such as receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), IL-6, and IL-6 soluble receptor (IL-6sR). In this experiment, we investigated the changes in serum levels of soluble RANKL (sRANKL), OPG, IL-6, and IL-6sR in patients with glucocorticoid-induced osteoporosis treated with hPTH (1-34). Fifty-one postmenopausal women with glucocorticoid-induced osteoporosis were randomized to receive 12 months of 400 U hPTH (1-34) ( approximately 40 microg) daily and standard hormone replacement therapy, or hormone replacement therapy alone. Serum levels of sRANKL, OPG, IL-6, and IL-6sR were measured at baseline, 1 month, and every 3 months thereafter for a total of 24 months. hPTH (1-34) caused a rapid and significant increase in sRANKL within 1 month, and the levels remained elevated throughout the duration of therapy. IL-6 and IL-6sR increased significantly within 1 month, but returned to baseline levels more rapidly. In contrast, OPG was mildly suppressed beginning 6 months after hPTH therapy. These data support the hypothesis that hPTH (1-34) initially stimulates osteoblast maturation and function, which in turn leads to osteoclast activation and a gradual rebalancing of bone formation and resorption.

Aged↗