Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. Methods We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 μg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. Results New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-μg and 40-μg parathyroid hormone groups; the respective relative risks of fracture in the 20-μg and 40-μg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragili...

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(96)07088-2.pdf

Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures

ContextRaloxifene hydrochloride, a selective estrogen receptor modulator, prevents
bone loss in postmenopausal women, but whether it reduces fracture risk in
these women is not known.ObjectiveTo determine the effect of raloxifene therapy on risk of vertebral and
nonvertebral fractures.DesignThe Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter,
randomized, blinded, placebo-controlled trial.Setting and ParticipantsA total of 7705 women aged 31 to 80 years in 25 countries who had been
postmenopausal for at least 2 years and who met World Health Organization
criteria for having osteoporosis. The study began in 1994 and had up to 36
months of follow-up for primary efficacy measurements and nonserious adverse
events and up to 40 months of follow-up for serious adverse events.InterventionsParticipants were randomized to 60 mg/d or 120 mg/d of raloxifene or
to identically appearing placebo pills; in addition, all women received supplemental
calcium and cholecalciferol.Main Outcome MeasuresIncident vertebral fracture was determined radiographically at baseline
and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained
by interview at 6-month-interim visits. Bone mineral density was determined
annually by dual-energy x-ray absorptiometry.ResultsAt 36 months of the evaluable radiographs in 6828 women, 503 (7.4%)
had at least 1 new vertebral fracture, including 10.1% of women receiving
placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those
receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in
both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR],
0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95%
CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who
did and did not have prevalent fracture. Risk of nonvertebral fracture for
raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1
for both raloxifene groups combined). Compared with placebo, raloxifene increased
bone mineral density in the femoral neck by 2.1% (60 mg) and 2.4% (120 mg)
and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001
for all comparisons). Women receiving raloxifene had increased risk of venous
thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause
vaginal bleeding or breast pain and was associated with a lower incidence
of breast cancer.ConclusionsIn postmenopausal women with osteoporosis, raloxifene increases bone
mineral density in the spine and femoral neck and reduces risk of vertebral
fracture.

https://jamanetwork.com/journals/jama/articlepdf/191242/JOC90496.pdf

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial

Context Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis.

https://www.osteos.org.lb/admin/uploads/VertNA-JAMA.pdf

Effects of Risedronate Treatment on Vertebral and Nonvertebral Fractures in Women With Postmenopausal Osteoporosis: A Randomized Controlled Trial

Context.—Alendronate sodium reduces fracture risk in
postmenopausal women who have vertebral fractures, but its effects on
fracture risk have not been studied for women without vertebral
fractures.Objective.—To test the hypothesis that 4 years of
alendronate would decrease the risk of clinical and vertebral fractures
in women who have low bone mineral density (BMD) but no vertebral
fractures.Design.—Randomized, blinded, placebo-controlled trial.Setting.—Eleven community-based clinical research centers.Subjects.—Women aged 54 to 81 years with a femoral neck BMD
of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no
vertebral fracture; 4432 were randomized to alendronate or placebo and
4272 (96%) completed outcome measurements at the final visit (an
average of 4.2 years later).Intervention.—All participants reporting calcium intakes of
1000 mg/d or less received a supplement containing 500 mg of calcium
and 250 IU of cholecalciferol. Subjects were randomly assigned to
either placebo or 5 mg/d of alendronate sodium for 2 years followed by
10 mg/d for the remainder of the trial.Main Outcome Measures.—Clinical fractures confirmed
by x-ray reports, new vertebral deformities detected by morphometric
measurements on radiographs, and BMD measured by dual x-ray
absorptiometry.Results.—Alendronate increased BMD at all sites studied
(P<.001) and reduced clinical fractures from 312 in the
placebo group to 272 in the intervention group, but not significantly
so (14% reduction; relative hazard [RH], 0.86; 95% confidence
interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by
36% in women with baseline osteoporosis at the femoral neck (>2.5
SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82;
treatment-control difference, 6.5%; number needed to treat [NNT],
15), but there was no significant reduction among those with higher BMD
(RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of
radiographic vertebral fractures by 44% overall (relative risk, 0.56;
95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60).
Alendronate did not increase the risk of gastrointestinal or other
adverse effects.Conclusions.—In women with low BMD but without vertebral
fractures, 4 years of alendronate safely increased BMD and decreased
the risk of first vertebral deformity. Alendronate significantly
reduced the risk of clinical fractures among women with osteoporosis
but not among women with higher BMD.

/pdf/effect-of-alendronate-on-risk-of-fracture-in-women-with-low-8gp9ew0eix.pdf

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.

Background Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed. Methods We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements. Results The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (±SE) differences in bone...

/pdf/effect-of-oral-alendronate-on-bone-mineral-density-and-the-5gpq20qwy7.pdf

Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis

/pdf/effect-of-oral-alendronate-on-bone-mineral-density-and-the-391ba13yc4.pdf

Raksha V. Shah

Papers

Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis

Effect of Oral Alendronate on Bone Mineral Density and the Incidence of Fractures in Postmenopausal Osteoporosis