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Research · Medication

Bisphosphonates

Cochrane reviews and large trials found bisphosphonates cut spine, hip and other fractures in postmenopausal women with osteoporosis, by about half for clinical spine fractures. Evidence in men was too thin to tell, and pooled trials found no drop in deaths. Atypical thigh fractures rose with years of use, jaw osteonecrosis was rare, and infusions often caused short flu-like reactions.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Alendronate, risedronate, ibandronate and zoledronic acid (Reclast) are FDA-approved to treat or prevent osteoporosis in postmenopausal women. Alendronate, risedronate and zoledronic acid are also approved for osteoporosis in men, osteoporosis from steroid medicines and Paget's disease of bone. Zoledronic acid at higher doses under other brand names is used in cancer, which this page does not cover.
Also called
alendronate, Fosamax, Fosamax Plus D, Binosto, risedronate, Actonel, Atelvia, ibandronate, Boniva, zoledronic acid, zoledronate, Reclast, osteoporosis drugs
Taken for
osteoporosis, osteopenia, preventing fractures, hip fracture, spine fracture, bone density, bone loss from steroids, Paget's disease of bone, living longer after a hip fracture

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help5

Reported risks11

What people take it for, and what was found

Shown to help5

StrongStudied in women

Fractures in postmenopausal women with osteoporosis

Shown to cut fractures in postmenopausal women with osteoporosis, with clinical spine fractures about 55% lower on alendronate, or 2.7 fewer per 100 women.

Compared with placebo or no treatment [1]; placebo [2][3][4]; placebo and other osteoporosis drugs [5]

The numbers and sources
Effect
In higher-risk women, alendronate lowered clinical vertebral fractures (RR 0.45, 95% CI 0.28 to 0.73, 2.7% fewer), non-vertebral fractures (RR 0.80, 2.8% fewer), hip fractures (RR 0.49, 1.0% fewer) and wrist fractures (RR 0.54, 1.8% fewer) [1]. Risedronate 5 mg a day lowered non-vertebral fractures (RR 0.80, 95% CI 0.72 to 0.90, 2% fewer) and hip fractures (RR 0.73, 1% fewer) [2]. Yearly zoledronic acid lowered spine fractures seen on x-ray from 10.9% to 3.3% over 3 years (RR 0.30, 95% CI 0.24 to 0.38) and hip fractures from 2.5% to 1.4% (HR 0.59), with 25% fewer non-vertebral fractures [3]. Daily and intermittent ibandronate lowered new spine fractures by 62% and 50% [4]. In a network meta-analysis, alendronate, risedronate and zoledronate each lowered hip, spine and non-vertebral fractures, while ibandronate lowered spine fractures only, with lower efficacy [5].
Population
7,375 higher-risk women in 20 alendronate trials of 1 to 3 years [1]; 14,354 higher-risk women in 9 risedronate trials [2]; 7,765 women, mean age 73 [3]; 2,946 women [4]; 193,987 postmenopausal women in 107 trials [5].
Sources
[1], [2], [3], [4], [5]
Caveats
Many trials in [1] and [2] had unclear or high risk of bias, and most certainty ratings were low to moderate. Risedronate's effect on clinical spine fractures could not be estimated because no events were reported [2].
ModerateStudied in women

Fractures in lower-risk women and women with osteopenia

Shown to lower spine and other fractures in lower-risk postmenopausal women, with 15 women with osteopenia treated with zoledronate for 6 years per fracture prevented.

Compared with placebo or no treatment [1]; placebo [2][6]

The numbers and sources
Effect
In lower-risk women, alendronate lowered clinical vertebral fractures (RR 0.45, 95% CI 0.25 to 0.84, 1.4% fewer) and non-vertebral fractures (RR 0.83, 1.6% fewer), with no clear difference in hip fractures (RR 0.76, 95% CI 0.43 to 1.32) or wrist fractures [1]. For risedronate in lower-risk women, effects on fractures were uncertain [2]. In women aged 65 or older with osteopenia, a fragility fracture occurred in 122 on zoledronate and 190 on placebo over 6 years (HR 0.63, 95% CI 0.50 to 0.79), a number needed to treat of 15 [6].
Population
10,057 lower-risk women in 16 alendronate trials of 1 to 5 years [1]; 989 women in 4 risedronate trials [2]; 2,000 women aged 65 or older with osteopenia, median 10-year hip fracture risk 2.3% [6].
Sources
[1], [2], [6]
Caveats
Low-certainty evidence in [1]. The osteopenia result rests on one trial [6].
Limited

New fractures and survival after a hip fracture

One trial found yearly zoledronic acid after hip fracture surgery lowered new fractures, 8.6% against 13.9%, and deaths, 9.6% against 13.3%, over about 2 years.

Compared with placebo, with calcium and vitamin D in both groups [7]

The numbers and sources
Effect
New clinical fractures occurred in 8.6% on zoledronic acid and 13.9% on placebo, a 35% reduction. New clinical spine fractures were 1.7% against 3.8%, and non-vertebral fractures 7.6% against 10.7%. Deaths from any cause were 9.6% against 13.3%, 28% fewer [7].
Population
2,127 adults, mean age 74.5, given the first infusion within 90 days of hip fracture repair, median follow-up 1.9 years [7].
Sources
[7]
Caveats
One trial. The pooled analysis of mortality below did not confirm a drop in deaths across trials [8].
Why limited
This rests on one trial, of 2,127 people. Strength counts independent studies that agree, so one trial is limited at any size.
Strong

Bone density in people taking steroid tablets

Shown to raise spine bone density more than placebo or calcium and vitamin D in people on steroid tablets, though less than teriparatide. Trials were too small to judge fractures.

Compared with placebo or calcium and vitamin D [10]; teriparatide and denosumab [10][11]

The numbers and sources
Effect
Every osteoporosis drug raised lumbar spine bone density more than placebo or calcium and vitamin D. Teriparatide raised it more than alendronate (effect size 3.8), risedronate (4.0) and zoledronate (2.4), and zoledronate and denosumab more than oral bisphosphonates [10]. A second network meta-analysis found alendronate, risedronate, etidronate and zoledronate all raised bone density, with teriparatide and denosumab ahead at the spine and femoral neck [11].
Population
5,260 adults on oral glucocorticoids in 31 studies, 72.5% women [10]; 2,877 patients in 11 trials [11].
Sources
[10], [11]
Caveats
Bone density is a stand-in for fractures, and the included studies were underpowered for fractures [10].
ModerateVery common

Paget's disease of bone

Shown to relieve bone pain in Paget's disease more often than placebo, 31% against 9%, with one zoledronic acid infusion normalizing alkaline phosphatase in 89% at 6 months.

Compared with placebo and other bisphosphonates [12]; risedronate [13]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Bone pain disappeared in 31% on a bisphosphonate and 9% on placebo (RR 3.42, 95% CI 1.31 to 8.90), a number needed to treat of 5. Fractures did not clearly differ. Zoledronate relieved pain more often than pamidronate or risedronate in single trials [12]. In two 6-month trials, one 5 mg infusion of zoledronic acid normalized serum alkaline phosphatase in 89% against 58% on risedronate 30 mg daily for 2 months, and a therapeutic response was seen in 96% against 74% [13].
Population
3,168 people in 20 trials, mean age 66 to 74, 51% to 74% men, mostly with raised alkaline phosphatase [12]; 349 adults with moderate to severe Paget's disease, mean age 70 [13].
Sources
[12], [13]
Caveats
Moderate-quality evidence for pain, and mean follow-up was 6 months [12]. Treating to normalize alkaline phosphatase did not improve pain or quality of life over treating symptoms [12].

Mixed results1

LimitedStudied in women

Continuing alendronate past 5 years

One trial found women who stopped alendronate after 5 years had the same non-vertebral fracture rate as those who continued, but more clinical spine fractures, 5.3% against 2.4%.

Compared with switching to placebo after 5 years [14]

The numbers and sources
Effect
Over 5 more years, non-vertebral fractures were 19% in women who continued and 18.9% in those who switched to placebo (RR 1.00, 95% CI 0.76 to 1.32). Clinical spine fractures were 2.4% against 5.3% (RR 0.45, 95% CI 0.24 to 0.85), and spine fractures on x-ray did not differ. Hip bone density fell 2.4% more after stopping [14].
Population
1,099 postmenopausal women who had taken alendronate for a mean 5 years [14].
Sources
[14]
Caveats
Fracture was an exploratory outcome. One trial.

Not shown to help2

Moderate

Death from any cause

Not shown to lower deaths across pooled placebo-controlled trials of bisphosphonates or of zoledronate alone.

Compared with placebo [8]

The numbers and sources
Effect
Bisphosphonate trials showed no significant association with overall mortality (RR 0.95, 95% CI 0.86 to 1.04), nor did zoledronate trials (RR 0.88, 95% CI 0.68 to 1.13), with some heterogeneity among the zoledronate trials (I² 48.2%) [8].
Population
42,867 people in 21 bisphosphonate trials, 13,870 of them in 6 zoledronate trials [8].
Sources
[8]
Caveats
Trials were designed around fractures, not deaths. One zoledronic acid trial after hip fracture found fewer deaths [7].
ModerateStudied in men

Fractures in men

Not shown to lower fractures in men over two years of use, because trials recorded too few fractures to tell. A Cochrane review called the effect very uncertain.

Compared with placebo [9]

The numbers and sources
Effect
Hip fractures occurred in 2 of 875 men on a bisphosphonate and 2 of 760 on placebo (RR 0.73, 95% CI 0.06 to 8.51). Symptomatic spine fractures were 5 of 1,021 against 7 of 855 (RR 0.49, 95% CI 0.14 to 1.74), and other fractures 25 of 1,130 against 19 of 913 (RR 0.78, 95% CI 0.42 to 1.45) [9].
Population
2,548 men aged 50 or older in 7 placebo-controlled bisphosphonate trials, average age 52 to 73 [9].
Sources
[9]
Caveats
Very low certainty evidence, with few events and possible selective reporting [9]. The FDA approvals for men rest on bone density gains, not fracture reduction.

Doses studied

The Cochrane alendronate analysis used 10 mg a day or 70 mg a week [1], and the risedronate analysis 5 mg a day [2]. Zoledronic acid was given as a 5 mg infusion once a year [3][7] or every 18 months [6]. The ibandronate trial used 2.5 mg a day or 20 mg every other day for 12 doses every 3 months [4]. In Paget's disease, one 5 mg zoledronic acid infusion was compared with risedronate 30 mg a day for 2 months [13], and the alendronate label gives 40 mg a day for 6 months [15]. The extension trial used alendronate 5 or 10 mg a day [14].

Risks

Reported risks8

ModerateVery common

Flu-like reaction after an infusion

Shown to cause fever, aches and flu-like symptoms within 3 days of a zoledronic acid infusion, with fever in 18% against 5% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the main osteoporosis trial, fever was reported in 17.9% on zoledronic acid and 4.6% on placebo, muscle pain in 11.7% against 3.7%, and influenza-like illness in 8.8% against 2.7%. Most symptoms began within 3 days and resolved within 3 days. When acetaminophen was given, fever fell to 7%, and symptoms became less frequent with later doses [13]. In Paget's disease, zoledronate raised transient fever or fatigue against placebo (RR 2.57, 95% CI 1.21 to 5.44) [12].
Population
7,714 women in the main osteoporosis trial [13]; 176 people in one Paget's trial [12].
Sources
[13], [12]
Caveats
Applies to the infusion. Oral bisphosphonates were not linked to this reaction in these sources.
ModerateVery common

Lower blood calcium

Shown to lower blood calcium slightly, with mild drops in 18% on alendronate against 12% on placebo. The zoledronic acid label calls low calcium a significant risk in Paget's disease.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Mild, transient, symptom-free drops in serum calcium occurred in about 18% on alendronate and 12% on placebo, and calcium fell about 2% from baseline in the first month. Drops below 8.0 mg/dL were similar in both groups [15]. After zoledronic acid, about 0.2% of women with osteoporosis had calcium below 7.5 mg/dL, and about 21% of people with Paget's disease had calcium below 8.4 mg/dL at 9 to 11 days [13].
Population
Alendronate controlled trials [15]; zoledronic acid osteoporosis and Paget's trials [13].
Sources
[15], [13]
Caveats
Both labels require low calcium and vitamin D shortage to be corrected first [15][13].
StrongCommon

Atrial fibrillation

Shown to raise serious atrial fibrillation in pooled trials, about 1.4 to 1.5 times the odds, 1.3% against 0.4% in the main zoledronic acid trial. Observational studies disagreed.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Serious atrial fibrillation was more frequent on bisphosphonates in pooled trials (OR 1.47, 95% CI 1.01 to 2.14), but all atrial fibrillation events were not (OR 1.14, 95% CI 0.96 to 1.36) [19]. A second meta-analysis found more serious atrial fibrillation in trials (OR 1.40, 95% CI 1.02 to 1.93) and no rise in stroke or cardiovascular death [20]. In the zoledronic acid label trial, serious atrial fibrillation occurred in 1.3% (50 of 3,862) against 0.4% (17 of 3,852) [13]. Pooled observational studies found no link in one analysis (OR 1.04, 95% CI 0.92 to 1.16) [21] and a small one in another (OR 1.17, 95% CI 1.01 to 1.36) [22].
Population
4 trial datasets [19]; 41,375 people in 6 trials and 149,856 in 6 observational studies [20]; 7,714 women [13]; 266,761 patients in 7 studies [21]; 12 observational studies [22].
Sources
[19], [20], [13], [21], [22]
Caveats
The trial signal rests mostly on zoledronic acid. Observational studies had high heterogeneity [22].
ModerateStudied in womenCommon

Kidney function after zoledronic acid

The label warns zoledronic acid can impair kidney function, with a short-lived creatinine rise within 10 days in 1.8% against 0.8% on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
A transient rise in serum creatinine within 10 days of dosing occurred in 1.8% on zoledronic acid and 0.8% on placebo and resolved without treatment. Changes in creatinine clearance over 3 years and rates of kidney failure were comparable to placebo. The label reports rare acute kidney failure and contraindicates it below a creatinine clearance of 35 mL/min [13].
Population
Women in the main osteoporosis trial, which excluded creatinine clearance under 30 mL/min [13].
Sources
[13]
Caveats
People with poorer kidney function were excluded from the trial.
ModerateUncommon

Atypical thigh bone fractures

Linked to rare atypical thigh bone fractures that rose with years of use and fell quickly after stopping. The label warns of them.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Bisphosphonate use was linked to subtrochanteric, femoral shaft and atypical femur fractures (adjusted RR 1.70, 95% CI 1.22 to 2.37), and 1.62 with at least 5 years of use [16]. Among 196,129 women on bisphosphonates, 277 had an atypical femur fracture. Against under 3 months of use, the hazard ratio was 8.86 at 3 to 5 years and 43.51 at 8 years or more. Asian women had 4.84 times the risk of White women. Over 3 years in White women, 149 hip fractures were prevented for every 2 atypical fractures, and in Asian women 91 for 8 [17]. The alendronate label warns of atypical low-energy femur fractures [15].
Population
11 observational studies [16]; 196,129 women aged 50 or older followed up to 10 years [17].
Sources
[16], [17], [15]
Caveats
Observational, with high heterogeneity in [16]. The 277 cases in [17] were counted over a decade of follow-up.
LimitedUncommon

Eye inflammation

Case reports and trial counts link bisphosphonates to rare eye inflammation such as uveitis, about 0.2% on zoledronic acid in trials. Cohort studies disagreed.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In the zoledronic acid osteoporosis trials, iritis, uveitis or episcleritis developed in less than 0.1% to 0.2% of treated patients and 0% to less than 0.1% on placebo, and 1.1% against 0% in the prevention trial [13]. A review found mostly case reports, some with recurrence on rechallenge, and three cohort studies with conflicting results [23].
Population
Zoledronic acid trial populations [13]; published case reports and cohort studies [23].
Sources
[13], [23]
Caveats
Trials were not powered for rare events [23].
ModerateRare

Osteonecrosis of the jaw

Linked to rare jaw bone death, estimated at 0.001% to 0.01% of people treated for osteoporosis, far below rates in cancer doses. The label warns of it.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
In people treated for osteoporosis, osteonecrosis of the jaw was estimated at 0.001% to 0.01%, marginally above the general population rate of under 0.001%. With oncology doses it was 1% to 15%. Risk factors included tooth extraction and oral surgery, glucocorticoids, poor oral hygiene and diabetes [18]. No cases occurred in the alendronate Cochrane trials [1] or the post hip fracture trial [7].
Population
A systematic review of studies from 2003 to 2014 [18]; trial populations [1][7].
Sources
[18], [1], [7], [15]
Caveats
Too rare to measure in trials. Estimates come from observational data.
LimitedHow often is not known

Interactions with calcium, antacids, aspirin and some other drugs

The labels warn that calcium and antacids block alendronate absorption, aspirin added gut side effects, and aminoglycosides or loop diuretics may lower calcium further with zoledronic acid.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Calcium supplements, antacids and oral medicines with multivalent cations interfere with alendronate absorption. Upper gastrointestinal events were more frequent with alendronate above 10 mg a day plus aspirin. In a 3-year trial where most people took NSAIDs, upper gastrointestinal events were similar on alendronate and placebo [15]. The zoledronic acid label advises caution with aminoglycosides, which may lower calcium for prolonged periods, and with loop diuretics, which may raise the risk of low calcium [13].
Population
Label statements and trial data [15][13].
Sources
[15], [13]
Caveats
Mostly label warnings, not measured rates.

Mixed results3

ModerateCommon

Upper gut irritation with tablets

Mixed results: the alendronate label warns of esophageal irritation and ulcers, while pooled trials found gut side effects about as frequent as on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In US and multinational label trials, abdominal pain was 6.6% on alendronate 10 mg and 4.8% on placebo, and esophageal ulcer 1.5% against 0.0%. In the larger Fracture Intervention Trial, abdominal pain was 1.5% in both groups. The label reports esophagitis, ulcers and erosions, rarely with stricture or perforation, more with lying down after a dose [15]. The Cochrane review found alendronate may make little or no difference to gastrointestinal adverse events [1]. In Paget's disease trials, mild gastrointestinal events were 64% against 48% (RR 1.32, 95% CI 0.91 to 1.92) [12].
Population
196 and 3,236 women on alendronate in label trials [15]; trial populations in [1] and [12].
Sources
[15], [1], [12]
Caveats
Label tables count only events the investigators judged drug related.
LimitedHow often is not known

Bone, joint and muscle pain

The label warns of severe, sometimes incapacitating bone, joint or muscle pain reported after approval, while placebo-controlled alendronate trials found similar rates.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The alendronate label reports postmarketing cases of severe bone, joint or muscle pain beginning a day to months after starting, mostly relieved after stopping, with some recurrence on rechallenge. In its placebo-controlled trials, the share with these symptoms was similar on alendronate and placebo [15]. In the main zoledronic acid trial, bone pain was 5.8% against 2.3% on placebo [13].
Population
Postmarketing reports and trial populations [15][13].
Sources
[15], [13]
Caveats
Postmarketing reports cannot give a rate.
ModerateHow often is not known

Esophageal cancer

Mixed results: a meta-analysis linked oral bisphosphonates to higher odds of esophageal cancer, while a large UK cohort found no difference.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across 7 studies, exposure to bisphosphonates was linked to esophageal cancer (OR 1.74, 95% CI 1.19 to 2.55), with high heterogeneity, a link for etidronate and none for alendronate [24]. In 41,826 bisphosphonate users and as many controls, esophageal cancer incidence was 0.48 and 0.44 per 1,000 person-years (adjusted HR 1.07, 95% CI 0.77 to 1.49) [25].
Population
19,700 esophageal cancer cases in 7 studies [24]; 83,652 people, 81% women, mean age 70, followed about 4.5 years [25].
Sources
[24], [25]
Caveats
All observational. Etidronate is not sold for osteoporosis in the US.

Checked, no increase found1

Strong

Serious adverse events overall

Not shown to raise serious adverse events against placebo in Cochrane reviews of alendronate, risedronate and bisphosphonates in men.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Serious adverse events were 29.2% on risedronate and placebo alike (RR 1.00, 95% CI 0.94 to 1.07) [2]. On alendronate they did not differ in lower-risk women (RR 1.08, 95% CI 0.82 to 1.43) and were fewer in higher-risk women (RR 0.75, 95% CI 0.59 to 0.96) [1]. In men they were 27.2% against 28.6% (RR 0.95, 95% CI 0.84 to 1.08) [9].
Population
9,435 women in 6 risedronate trials [2]; alendronate trial populations [1]; 2,457 men in 6 trials [9].
Sources
[2], [1], [9]
Caveats
Trials were not large enough to catch rare harms such as atypical fractures.

Possible, not studied in people1

Untested

Use in pregnancy

Not studied in people. Animal studies of alendronate found reduced pup survival and bone formation, and bisphosphonates stay in bone for years after stopping.

No study in people. This rests on animal studies, how it acts in the body.

The numbers and sources
Effect
The alendronate label states human data are insufficient. In rats, alendronate reduced survival after implantation and pup weight gain at under half the highest human dose, and reduced fetal bone formation at 3 times it, with maternal low calcium causing delivery problems. Because bisphosphonates are released from bone over years, the label notes a possible risk to a fetus if pregnancy follows a course of treatment [15].
Population
Rats and rabbits [15].
Sources
[15]
Caveats
Animal data and mechanism only.

Claims tested and not found

  1. That bisphosphonates lower overall death rates. Pooled placebo-controlled trials found no significant drop in mortality for bisphosphonates (RR 0.95) or zoledronate (RR 0.88) [8].
  2. That stopping alendronate after 5 years raises non-vertebral fractures. Women who switched to placebo had the same non-vertebral fracture rate as those who continued, 18.9% against 19% [14].
  3. That alendronate prevents hip fractures in lower-risk women. Hip fractures did not clearly differ from placebo in primary prevention trials (RR 0.76, 95% CI 0.43 to 1.32) [1].
  4. That bisphosphonate tablets cause more stomach and gut problems than placebo in trials. Pooled alendronate trials found little or no difference in gastrointestinal adverse events [1].

Sources

  1. Wells GA, Hsieh SC, Peterson J, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews. 2025. https://doi.org/10.1002/14651858.CD001155.pub3
  2. Wells GA, Hsieh SC, Zheng C, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews. 2022. https://doi.org/10.1002/14651858.CD004523.pub4
  3. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New England Journal of Medicine. 2007. https://doi.org/10.1056/NEJMoa067312
  4. Delmas PD, Recker RR, Chesnut CH, et al. Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study. Osteoporosis International. 2004. https://doi.org/10.1007/s00198-004-1602-9
  5. Barrionuevo P, Kapoor E, Asi N, et al. Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis. The Journal of Clinical Endocrinology and Metabolism. 2019. https://doi.org/10.1210/jc.2019-00192
  6. Reid IR, Horne AM, Mihov B, et al. Fracture Prevention with Zoledronate in Older Women with Osteopenia. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1808082
  7. Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. New England Journal of Medicine. 2007. https://doi.org/10.1056/NEJMoa074941
  8. Cummings SR, Lui LY, Eastell R, Allen IE. Association Between Drug Treatments for Patients With Osteoporosis and Overall Mortality Rates: A Meta-analysis. JAMA Internal Medicine. 2019. https://doi.org/10.1001/jamainternmed.2019.2779
  9. Braten LC, Suter C, Johnston RV, et al. Pharmacological therapies for the prevention of fractures in men. Cochrane Database of Systematic Reviews. 2026. https://doi.org/10.1002/14651858.CD014707.pub2
  10. Yavropoulou MP, Ter Wee MM, Naciu AM, et al. Effectiveness of anti-osteoporotic medications in the management of glucocorticoid-induced osteoporosis: a systematic review and network meta-analysis on behalf of the ECTS clinical action group. European Journal of Endocrinology. 2026. https://doi.org/10.1093/ejendo/lvag147
  11. Dong L, Jiang L, Xu Z, et al. Denosumab, teriparatide and bisphosphonates for glucocorticoid-induced osteoporosis: a Bayesian network meta-analysis. Frontiers in Pharmacology. 2024. https://doi.org/10.3389/fphar.2024.1336075
  12. Corral-Gudino L, Tan AJ, del Pino-Montes J, et al. Bisphosphonates for Paget's disease of bone in adults. Cochrane Database of Systematic Reviews. 2017. https://doi.org/10.1002/14651858.CD004956.pub3
  13. U.S. Food and Drug Administration. RECLAST (zoledronic acid) injection, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9b3737-9ce6-4a89-b76e-6aab79eba9cf
  14. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006. https://doi.org/10.1001/jama.296.24.2927
  15. U.S. Food and Drug Administration. FOSAMAX (alendronate sodium) tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14e931fd-2c5f-4d90-b7db-5980706f4a56
  16. Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. Journal of Bone and Mineral Research. 2013. https://doi.org/10.1002/jbmr.1893
  17. Black DM, Geiger EJ, Eastell R, et al. Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. New England Journal of Medicine. 2020. https://doi.org/10.1056/NEJMoa1916525
  18. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. Journal of Bone and Mineral Research. 2015. https://doi.org/10.1002/jbmr.2405
  19. Loke YK, Jeevanantham V, Singh S. Bisphosphonates and atrial fibrillation: systematic review and meta-analysis. Drug Safety. 2009. https://doi.org/10.2165/00002018-200932030-00004
  20. Sharma A, Chatterjee S, Arbab-Zadeh A, et al. Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis. Chest. 2013. https://doi.org/10.1378/chest.13-0675
  21. Kim SY, Kim MJ, Cadarette SM, Solomon DH. Bisphosphonates and risk of atrial fibrillation: a meta-analysis. Arthritis Research and Therapy. 2010. https://doi.org/10.1186/ar2938
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