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Felicia Cosman

Publications and source records attributed to Felicia Cosman.

18 recordsLinked to original sources
PubMed2007

Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium.

UNLABELLED: Using bone histomorphometry, we found that a 1-month treatment with PTH(1-34) [hPTH(1-34)] stimulated new bone formation on cancellous, endocortical, and periosteal bone surfaces. Enhanced bone formation was associated with an increase in osteoblast apoptosis. INTRODUCTION: The precise mechanisms by which hPTH(1-34) increases bone mass and improves bone structure are unclear. Using bone histomorphometry, we studied the early effects of treating postmenopausal women with osteoporosis with hPTH(1-34). MATERIALS AND METHODS: Tetracycline-labeled iliac crest bone biopsies were obtained from 27 postmenopausal women with osteoporosis who were treated for 1 month with hPTH(1-34), 50 microg daily subcutaneously. The results were compared with tetracycline-labeled biopsies from a representative control group of 13 postmenopausal women with osteoporosis. RESULTS: The bone formation rate on the cancellous and endocortical surfaces was higher in hPTH(1-34)-treated women than in control women by factors of 4.5 and 5.0, respectively. We also showed a 4-fold increase in bone formation rate on the periosteal surface, suggesting that hPTH(1-34) has the potential to increase bone diameter in humans. On the cancellous and endocortical surfaces, the increased bone formation rate was primarily caused by stimulation of formation in ongoing remodeling units, with a modest amount of increased formation on previously quiescent surfaces. hPTH(1-34)-stimulated bone formation was associated with an increase in osteoblast apoptosis, which may reflect enhanced turnover of the osteoblast population and may contribute to the anabolic action of hPTH(1-34). CONCLUSIONS: These findings provide new insight into the cellular basis by which hPTH(1-34) improves cancellous and cortical bone architecture and geometry in patients with osteoporosis.

Aged↗
PubMed2006

Effects of cyclic vs. daily treatment with human parathyroid hormone (1-34) on murine bone structure and cellular activity.

Previously, we demonstrated that the human parathyroid hormone (1-34) fragment (hPTH(1-34)) increased bone strength in proportion to its effects on BMD and cortical bone structure in the murine femur by comparing cyclic vs. daily administration of hPTH(1-34). Both cyclic and daily regimens increased vertebral BMD similarly at 7 weeks. Here, we have examined the effects of daily and cyclic PTH regimens on bone structure and cellular activity by static and dynamic histomorphometry. Twenty-week-old, intact female C57BL/J6 mice were treated with the following regimens (n=7 for each group): daily injection with vehicle for 7 weeks [control]; daily injection with hPTH(1-34) (40 microg/kg/day) for 7 weeks [daily PTH]; and daily injection with hPTH(1-34) (40 microg/kg/day) and vehicle alternating weekly for 7 weeks [cyclic PTH]. At days 9 and 10, and 2 and 3 prior to euthanasia, calcein (10 mg/kg) was injected subcutaneously. At the end of study, the lumbar vertebrae 1-3 and the left femora were excised, cleaned, and processed for histomorphometry. In the lumbar vertebrae, daily and cyclic PTH regimens significantly increased cancellous bone volume (BV/TV), trabecular number, trabecular osteoclast and osteoblast perimeters, trabecular mineral apposition rate (MAR) and bone formation rate (BFR), and periosteal MAR and BFR compared to control, with no significant difference between the two PTH-treated groups. Increased trabecular tunneling was observed in both PTH-treated groups. Both regimens tended to increase vertebral cortical bone formation parameters with the effects at the periosteum site being more marked than those at the endosteum site, resulting in a significant increase in cortical width. In the femur, the effects of cyclic PTH on BV/TV, trabecular width and number, trabecular and endocortical osteoblast and osteoclast perimeters, cortical width, and trabecular and periosteal BFR were less marked than those of daily PTH. A cyclic PTH regimen was as effective as a daily regimen in improving cancellous and cortical bone microarchitecture and cellular activity in the murine vertebra.

Animals↗
PubMed2006

Anabolic therapy for osteoporosis: parathyroid hormone.

Recombinant human parathyroid hormone (PTH 1-34) is the only anabolic agent currently approved for the treatment of osteoporosis. The term anabolic is based on mechanism of action. PTH stimulates bone formation, in contrast to antiresorptive agents, which reduce bone resorption and formation. Recent investigations involving the PTH(1-34) and PTH(1-84) peptides, alone and in combination or sequential regimens with antiresorptive agents, have provided a greater understanding of the place of PTH in the armamentarium against osteoporosis. These studies indicate that adding a bisphosphonate to PTH in previously untreated individuals does not produce additional bone benefit; however, sequential use of PTH followed-up by an antiresorptive agent is highly effective at increasing bone mineral density. Adding PTH after an antiresorptive agent also produces substantial bone density increments, though the magnitude of bone density increase may differ for different antiresorptive agents. PTH can repair underlying micro-architectural defects in bone, improve bone mass substantially, and perhaps change macro-architecture and geometry of bone. There are still many unanswered questions regarding PTH treatment of osteoporosis, including the optimal duration of treatment, optimal dosing regimen, mechanism of resistance to its effect after 18-24 months, and the effect of subsequent rechallenge.

Journal Article↗
PubMed2005

A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide.

UNLABELLED: We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short-term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation. INTRODUCTION: Iliac crest biopsy, with histomorphometric evaluation, provides important information about cellular activity in bone. However, to obtain longitudinal information, repeat biopsies must be performed. In this study, we show the capability to obtain short-term longitudinal information on bone formation in a single biopsy using a novel, quadruple labeling technique. MATERIALS AND METHODS: Two tetracycline labels were administered using a standard 3 days on, 12 days off, 3 days on format. Four weeks later, the tetracycline labeling was repeated using the same schedule but with a different tetracycline that can be distinguished from the first by its color under fluorescent light. Iliac crest biopsies were performed 1 week later and prepared undecalcified for histomorphometry. Indices of bone formation 1 month apart were measured and calculated using the two sets of labels. We used this method to investigate the early effects of teriparatide [hPTH(1-34)] treatment on bone formation. The results were compared with those from a group of control subjects who were quadruple-labeled, but did not receive hPTH(1-34). RESULTS: Treatment with hPTH(1-34) dramatically stimulated bone formation on cancellous and endocortical surfaces. This was achieved by both an increase in the linear rate of matrix apposition and extension of the bone-forming surface. New bone was deposited on previously quiescent surfaces (i.e., modeling-based formation), but a proportion of this could occur by encroachment from adjacent resorption cavities. CONCLUSIONS: A single transiliac crest bone biopsy, after sequential administration of two sets of tetracycline labels is a useful approach to study the short-term effects of anabolic agents on human bone. One month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation.

Anabolic Agents↗
PubMed2005

Effects of cyclic versus daily hPTH(1-34) regimens on bone strength in association with BMD, biochemical markers, and bone structure in mice.

UNLABELLED: We developed a cyclic PTH regimen with repeated cycles of 1-week on and off daily PTH injection and explored its effects on bone strength, BMD, bone markers, and bone structure in mice. Cyclic protocols produced 60-85% of the effects achieved by daily protocols with 57% of the total PTH given, indicating more economic use of PTH. The study supports further exploration of cyclic PTH regimens for the treatment of osteoporosis. INTRODUCTION: To minimize the cost and the catabolic action of hPTH(1-34), a cyclic PTH regimen with repeated 3-month cycles of on-and-off daily injection of hPTH(1-34) was developed in humans and shown to be as effective as a daily regimen in increasing vertebral BMD. However, changes in BMD may not adequately predict changes in bone strength. A murine model was developed to explore the efficacy of a cyclic PTH regimen on bone strength in association with other bone variables. MATERIALS AND METHODS: Twenty-week-old, intact, female C57BL/J6 mice (n = 7/group) were treated with (1) daily injection with vehicle for 7 weeks (control); (2) daily injection with hPTH(1-34) (40 microg/kg/day) for 7 weeks (daily PTH); and (3) daily injection with hPTH(1-34) and vehicle alternating weekly for 7 weeks (cyclic PTH). BMD was measured weekly by DXA, and serum bone markers, bone structure, and strength were measured at 7 weeks. RESULTS: Daily and cyclic PTH regimens increased BMD at all sites by 16-17% and 9-12%, respectively (all p < 0.01). The most dramatic effect of cyclic PTH occurred during the second week of treatment when PTH was off, with femoral and tibial BMD continuing to increase to the same extent as that produced by daily PTH. Both daily and cyclic PTH regimens significantly increased osteocalcin (daily, 330%; cyclic, 260%), mTRACP (daily, 145%; cyclic, 70%), femoral cortical width (daily, 23%; cyclic, 13%), periosteal circumference (daily, 5%; cyclic, 3.5%), and bone strength (max load: daily, 48%; cyclic, 28%; energy absorbed: daily, 103%; cyclic, 61%), respectively. Femoral bone strength was positively correlated with BMD, bone markers, and cortical structure. Neither regimen had an effect on vertebral bone strength. Although actual effects of cyclic PTH were 60-85% of those produced by daily PTH, the effects of cyclic PTH per unit amount administered were slightly greater than those of daily PTH for most measures. CONCLUSIONS: PTH-enhanced femoral bone strength is positively correlated with its effects on femoral BMD, bone markers, and bone structure. Cyclic PTH regimens represent a potential economic use of PTH and warrant further study.

Acid Phosphatase↗
PubMed2005

Daily and cyclic parathyroid hormone in women receiving alendronate.

BACKGROUND: We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to parathyroid hormone treatment and whether short, three-month cycles of parathyroid hormone therapy could be as effective as daily administration. METHODS: We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus parathyroid hormone (1-34) subcutaneously daily, continued alendronate plus parathyroid hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without parathyroid hormone, or alendronate alone for 15 months. RESULTS: In both parathyroid hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic parathyroid hormone, bone formation declined during cycles without parathyroid hormone and increased again during cycles with parathyroid hormone. Bone resorption increased in both parathyroid hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each parathyroid hormone group as compared with the alendronate group and no significant difference between parathyroid hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities. CONCLUSIONS: This study suggests that a regimen of three-month cycles of parathyroid hormone alternating with three-month cycles without parathyroid hormone causes the early phase of action of parathyroid hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with parathyroid hormone increase spinal bone mineral density.

Aged↗
PubMed2005

The prevention and treatment of osteoporosis: a review.

Osteoporosis is a disorder characterized by reduced bone strength, diminished bone density, and altered macrogeometry and microscopic architecture. Adult bone mass is the integral measurement of the bone mass level achieved at the peak minus the rate and duration of subsequent bone loss. There is clearly a genetic predisposition to attained peak bone mass, which occurs by a person's mid-20s. Bone loss with age and menopause are universal, but rates vary among individuals. Both peak bone mass and subsequent bone loss can be modified by environmental factors, such as nutrition, physical activity, and concomitant diseases and medications. Osteoporosis prevention requires adequate calcium and vitamin D intake, regular physical activity, and avoiding smoking and excessive alcohol ingestion. Risk of fracture determines whether medication is also warranted. A previous vertebral or hip fracture is the most important predictor of fracture risk. Bone density is the best predictor of fracture risk for those without prior adult fractures. Age, weight, certain medications, and family history also help establish a person's risk for osteoporotic fractures. All women should have a bone density test by the age of 65 or younger (at the time of menopause) if risk factors are present. Guidelines for men are currently in development. Medications include both antiresorptive and anabolic types. Antiresorptive medications--estrogens, selective estrogen receptor modulators (raloxifene), bisphosphonates (alendronate, risedronate, and ibandronate) and calcitonins--work by reducing rates of bone remodeling. Teriparatide (parathyroid hormone) is the only anabolic agent currently approved for osteoporosis in the United States. It stimulates new bone formation, repairing architectural defects and improving bone density. All persons who have had osteoporotic vertebral or hip fractures and those with a bone mineral density diagnostic of osteoporosis should receive treatment. In those with a bone mineral density above the osteoporosis range, treatment may be indicated depending on the number and severity of other risk factors.

Fractures, Bone↗
PubMed2005

Normal human osteoclasts formed from peripheral blood monocytes express PTH type 1 receptors and are stimulated by PTH in the absence of osteoblasts.

The prevailing view for many years has been that osteoclasts do not express parathyroid hormone (PTH) receptors and that PTH's effects on osteoclasts are mediated indirectly via osteoblasts. However, several recent reports suggest that osteoclasts express PTH receptors. In this study, we tested the hypothesis that human osteoclasts formed in vitro express functional PTH type 1 receptors (PTH1R). Peripheral blood monocytes (PBMC) were cultured on bone slices or plastic culture dishes with human recombinant RANK ligand (RANKL) and recombinant human macrophage colony-stimulating factor (M-CSF) for 16-21 days. This resulted in a mixed population of mono- and multi-nucleated cells, all of which stained positively for the human calcitonin receptor. The cells actively resorbed bone, as assessed by release of C-terminal telopeptide of type I collagen and the formation of abundant resorption pits. We obtained evidence for the presence of PTH1R in these cells by four independent techniques. First, using immunocytochemistry, positive staining for PTH1R was observed in both mono- and multi-nucleated cells intimately associated with resorption cavities. Second, PTH1R protein expression was demonstrated by Western blot analysis. Third, the cells expressed PTH1R mRNA at 21 days and treatment with 10(-7) M hPTH (1-34) reduced PTH1R mRNA expression by 35%. Finally, bone resorption was reproducibly increased by two to threefold when PTH (1-34) was added to the cultures. These findings provide strong support for a direct stimulatory action of PTH on human osteoclasts mediated by PTH1R. This suggests a dual regulatory mechanism, whereby PTH acts both directly on osteoclasts and also, indirectly, via osteoblasts.

Cell Differentiation↗
PubMed2005

Anabolic therapy for osteoporosis: parathyroid hormone.

Recombinant human parathyroid hormone (PTH 1-34) is the only anabolic agent currently approved for the treatment of osteoporosis. The term anabolic is based on mechanism of action. PTH stimulates bone formation, in contrast to antiresorptive agents, which reduce bone resorption and formation. Recent investigations involving the PTH(1-34) and PTH(1-84) peptides, alone and in combination or sequential regimens with antiresorptive agents, have provided a greater understanding of the place of PTH in the armamentarium against osteoporosis. These studies indicate that adding a bisphosphonate to PTH in previously untreated individuals does not produce additional bone benefit; however, sequential use of PTH followed-up by an antiresorptive agent is highly effective at increasing BMD. Adding PTH after an antiresorptive agent also produces substantial bone density increments, though the magnitude of bone density increase may differ for different antiresorptive agents. PTH can repair underlying micro-architectural defects in bone, improve bone mass substantially, and perhaps change macro-architecture and geometry of bone. There are still many unanswered questions regarding PTH treatment of osteoporosis, including the optimal duration of treatment, optimal dosing regimen, mechanism of resistance to its effect after 18-24 months, and the effect of subsequent rechallenge.

Bone Density Conservation Agents↗
PubMed2005

The effects of hormone replacement on the biomechanical properties of the uterosacral and round ligaments in the monkey model.

OBJECTIVE: The purpose of this study was to determine effects of ovariectomy (OVX) and conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA), or ethinyl estradiol plus norethindrone acetate (EE/NA) on biomechanics of uterosacral (USL) and round (RL) ligaments in postmenopausal (PMP) monkeys. STUDY DESIGN: This was a randomized, triple blind, placebo-controlled study. OVX monkeys received 12 months no treatment (Pbo) (n = 19), CEE/MPA (n = 19), or EE/NA (n = 21). USL and RL step strains and stress-relaxation data were curve-fitted, giving strain-dependent tensile modulus (TM) from 0% to 30%. RESULTS: (1) USL: TM for both treatment groups was greater than Pbo for strains from 0% to 12% (P < .04). (2) RL: TM for both treatment groups was smaller than Pbo for strains from 12% to 30% (P < .05). No differences were found between treatment regimens. CONCLUSION: CEE/MPA and EE/NA both affect functional biomechanical properties by increasing tensile stiffness in the USL and decreasing it in the RL.

Animals↗
PubMed2004

Males have larger skeletal size and bone mass than females, despite comparable body size.

UNLABELLED: Gender differences in fractures may be related to body size, bone size, geometry, or density. We studied this in 18-year-old males (n = 36) and females (n = 36) matched for height and weight. Despite comparable body size, males have greater BMC and BMD at the hip and distal tibia and greater tibial cortical thickness. This may confer greater skeletal integrity in males. INTRODUCTION: Gender differences in fractures may be related to body size, bone size, geometry, or density. We studied this in males (n = 36) and females (n = 36; mean age = 18 years) pair-matched for height and weight. MATERIALS AND METHODS: BMC, bone area (BA), and BMD were measured in the spine and hip using DXA. Distal tibia was measured by pQCT. RESULTS AND CONCLUSIONS: Males had a higher lean mass (92%) compared with females (79%). No gender differences were observed for vertebral BMC or vertebral height, although males had greater width and thus BA at the spine. Males had greater BMC and BA at the femoral neck and total femur (p < 0.02). Geometric variables of the hip including neck diameter and neck-axis length were also greater in males (p < 0.02). There was greater cross-sectional moment of inertia, safety factor, and fall index in males (all p < 0.02). Males had greater tibial BMC, volumetric BMD, and cortical area and thickness compared with females (p < 0.01), with both greater periosteal circumference (p = 0.011) and smaller endosteal circumference (p = 0.058). Statistically controlling for lean mass reduced gender differences, but males still had 8% higher hip BMD (p = 0.24) and 5.3% higher total tibial BMD (p = 0.05). A subset of males and females were matched (n = 14 pairs) for total hip BA. Males in this subset still had greater BMC and BMD at the total hip (p < 0.05) than females, despite similar BA. In summary, despite comparable body size, males have greater BMC and BMD than females at the hip and distal tibia but not at the spine. Differences in BMC and BMD were related to greater cortical thickness in the tibia. We conclude that differences in bone mass and geometry confer greater skeletal integrity in males, which may contribute to the lower incidence of stress and osteoporotic fractures in males.

Adolescent↗
PubMed2004

The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)].

Teriparatide, the active fragment of human parathyroid hormone (hPTH 1-34), is an anabolic agent for the treatment of osteoporosis. Important questions remain regarding management strategy beyond the recommended 18- to 24-month course of teriparatide treatment. We followed 21 men for up to 2 years after discontinuing teriparatide. Twelve men (57%) chose treatment with bisphosphonate immediately after teriparatide withdrawal, while 9 (43%) opted for no pharmacologic agent. At the end of 1 year lumbar spine bone density increased an additional 5.1+/-1.0% in the bisphosphonate group, while it declined by 3.7+/-1.7% in those on no medication (P<0.002). In six men who delayed initiation of bisphosphonate until 1 year after teriparatide withdrawal, their subsequent gains in the second year, 2.6+/-1.7%, still placed them below the peak gains they achieved on teriparatide. In contrast, the 12 men who began bisphosphonates immediately and continued treatment for the entire 2-year post-PTH period had continued gains at the lumbar spine, 8.9+/-1.5% above their post-PTH values (P=0.002). For the 4-year period, including 2 years of teriparatide and 2 years of bisphosphonate, the total gains at the lumbar spine were 23.6+/-2.9%. Men, who received bisphosphonate in only the 2nd year post-teriparatide, had cumulative gains of 11.1+/-3.4%. Three men who did not receive any bisphosphonate at any time during the post-PTH period had cumulative gains of only 5.5+/-3.7%. These findings suggest that the use of bisphosphonates following teriparatide is an important component of any strategy utilizing this anabolic drug for osteoporosis in men. The immediate use of bisphosphonates after teriparatide withdrawal may help to optimize gains in bone density at the lumbar spine.

Analysis of Variance↗
PubMed2004

Therapeutic potential of parathyroid hormone.

Teriparatide, recombinant human parathyroid hormone (1-34) (rhPTH [1-34]), is approved for the treatment of osteoporosis in men and postmenopausal women at high risk for fracture. The best candidates are those who have already had vertebral compression fractures (symptomatic or asymptomatic) or other osteoporosis-related fractures, or those who have very low bone mineral density, in the T score range of -3.5 or below. Teriparatide is the first anabolic drug approved by the US Food and Drug Administration for osteoporosis. It not only dramatically improves bone mass, but also restores bone microarchitecture and increases bone diameter. All of these mechanisms contribute to increasing bone strength and reducing the risk for osteoporosis-related fractures. Although PTH has been used in combination with other agents such as estrogens, calcitonin, and bisphosphonates, the relative benefit of the combined approach versus teriparatide alone for fracture risk reduction has not been shown. In fact, some data suggest that initiating PTH and alendronate together in previously untreated patients or pretreating patients for a short time with alendronate before initiating PTH may somewhat reduce the anabolic response to PTH. There are many unanswered questions regarding PTH, such as the optimal duration of treatment, the optimal sequence of medications for severe osteoporosis, the mechanism of resistance to effect after 18 to 24 months, the effect of subsequent rechallenge with PTH and, most importantly, surrogates to measure PTH effect.

Aged↗
PubMed2003

Selective estrogen-receptor modulators.

Tamoxifen is useful for adjuvant treatment of breast cancer and in some women for the prevention of breast cancer. The risk-benefit ratio in regard to the skeleton and perhaps other organ systems may very well be different for postmenopausal versus premenopausal women. In postmenopausal women, tamoxifen (20 mg/d) increased BMD in the spine and perhaps the hip; however, the effect on fracture risk is unclear. Therefore, for postmenopausal women with osteoporosis, consideration should be given to the addition of an agent that is shown to have efficacy against fractures (such as bisphosphonates), even while these women are on tamoxifen. For women at only modest or moderate risk, with bone density above the osteoporosis range (T score above -2.5) and no major fracture history, tamoxifen is probably adequate for 5 years of use. Potentially serious adverse effects include venous thromboembolism, uterine cancer, benign uterine disease, and cataracts. Raloxifene (60 mg/d) protects against vertebral fractures over 4 years in women with osteoporosis, produces small increases in bone mass of the spine, hip, and total body, and reduces bone turnover in postmenopausal women with or without osteoporosis. No significant effect has yet been demonstrated on nonvertebral fractures after 4 years of treatment. Raloxifene has the additional benefit of substantially reducing the risk of ER-positive invasive breast cancer and does not increase the risk of uterine disease. Raloxifene increases the risk of venous thromboembolic disease to the same degree as tamoxifen and estrogen. Therefore, SERMS and estrogens are generally contraindicated in women with a previous history of venous thromboembolism or those who are at significantly increased risk. Raloxifene is probably most useful in women who have osteoporosis (T score = -2.5) or who are at risk (T score less than -1.5 with clinical risk factors) in the middle menopausal period (age 55-65) or in the early menopausal period in women who have no significant hot flashes. At this stage in life, vertebral fractures are common, but hip fractures are not. Therefore, women who take raloxifene can expect a reduction in the likelihood of having a vertebral fracture, and possibly breast cancer. The lack of definitive efficacy against hip fracture is not a major deterrent to use of this agent in this age group because hip fracture risk is very low. Raloxifene might not be the treatment of choice for elderly women who are at particularly high risk of hip fracture.

Female↗
PubMed2003

Short-term urogenital effects of raloxifene, tamoxifen, and estrogen.

OBJECTIVE: The purpose of this study was to assess the urogenital effects of raloxifene, tamoxifen, conjugated equine estrogen, and placebo in healthy postmenopausal women. STUDY DESIGN: This randomized, double-blind, placebo-controlled study compared the urogenital effects of 0.625 mg of conjugated equine estrogen (n = 15 women), 20 mg of tamoxifen (n = 14 women), 60 mg of raloxifene, (n = 15 women), and placebo (n = 13 women). Evaluations at baseline and evaluations after 20 weeks receiving the drug included a pelvic examination with cytologic evaluation of vagina and urethra, pelvic organ prolapse quantitation, and urethral axis deflection by cotton swab test (only in patients with incontinence [33%]). RESULTS: Conjugated equine estrogen increased the maturation value of both urethral and vaginal cytologic condition (P =.002, P =.032, respectively). There was a decrease in vaginal maturation value in the raloxifene group (not significant). Two of 8 women in the conjugated equine estrogen group showed evidence of worsening prolapse by pelvic organ prolapse quantitation; the condition of 2 of 8 women improved. In the raloxifene, tamoxifen, and placebo groups 8 of 12 women, 4 of 13 women, and 2 of 11 women had worsening in prolapse scores, respectively, whereas none of the women had improvement. Increased cotton swab deflection was found in 3 of 5 women in the raloxifene group, in 5 of 8 women in the tamoxifen group, in 0 of 4 women in the placebo group, and in 0 of 2 women in the conjugated equine estrogen group. Seventy-five percent of the patients who received raloxifene and 60% of the patients who received tamoxifen had increases in prolapse by any measure (ie, pelvic organ prolapse quantitation or cotton swab or clinical assessment) compared with 18% of the patients in the placebo group and 22% of the patients in the conjugated equine estrogen group (P =.015), although symptoms did not differ among groups. CONCLUSION: Neither raloxifene nor tamoxifen improve cytohormonal effects in the vagina or urethra, whereas conjugated equine estrogen does. Raloxifene and tamoxifen appear to show worsening prolapse compared with conjugated equine estrogen and placebo. The clinical relevance of these effects is unknown and requires investigation.

Aged↗
PubMed2003

Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment.

Anabolic effects of PTH have been observed at several skeletal sites in humans by dual x-ray absorptiometry without differentiating between an actual increase in bone volume and an increase in mineral content within already established bone. The present study addressed this issue by evaluating the bone mineralization density distribution of iliac crest bone biopsies before and after PTH treatment for 18-36 months in men and women with osteoporosis using quantitative backscattered electron imaging. In cortical bone, pairwise comparison of the two biopsies before and after treatment revealed a reduction in the typical calcium concentration in men (-3.32%; P = 0.02, by paired t test), but no change in women, and the heterogeneity of mineralization increased in both males and females [+18.80% (P = 0.09) and +18.14% (P = 0.005), respectively]. In cancellous bone, there was no change in the typical calcium concentration, but there was a greater heterogeneity of mineralization in both men and women [+19.65% (P = 0.02) and +21.59% (P = 0.056), respectively] due to newly formed bone matrix. Small angle x-ray scattering performed on a subgroup of subjects revealed normal collagen/mineral structure. The findings confirm the observations that PTH stimulates skeletal remodeling, resulting in an increased percentage of newly formed bone matrix of lower mineral density.

Absorptiometry, Photon↗