This page shows what was measured, who it was measured in, and what that does not settle.
What Alendronic acid does in the body
Thinning, fragile bones that break more easily than they should
Bone is constantly dissolved and rebuilt. Alendronate sticks to bone mineral like a magnet, and it sticks hardest exactly where the demolition cells are working. When one of those cells dissolves the surface underneath it, it swallows the drug with the mineral. Inside the cell the drug blocks an enzyme the cell needs to keep its grip and its digestive machinery, so demolition slows and the builders catch up.
What happened in people
New morphometric vertebral fracture 8.0% against 15.0% over three years in 2027 women with a prior vertebral fracture, RR 0.53 (95% CI 0.41 to 0.68)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That the fracture benefit shown in women with a prior vertebral fracture transfers to women with only low bone density — the primary endpoint in that population was not met
Where it acts
The resorption pit under an osteoclast on a bone surface — the drug binds the mineral, and the cell swallows it while digging
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
6 registered substances share the start of this name, which is why a search for it can return more than one thing.
FDA substance registry · X1J18R4W8P · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 111 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
New morphometric vertebral fracture at 36 months
✓ The study showed what it set out to show
Who was studied
Fracture Intervention Trial, vertebral fracture arm (Black 1996)
Clinical fractures confirmed by radiograph report over a mean 4.2 years
✗ The study did not show it
Who was studied
Fracture Intervention Trial, clinical fracture arm (Cummings 1998)
How many people
4432
Study design
Phase 3, randomised, blinded, placebo-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
272 against 312 events; relative hazard 0.86 (95% CI 0.73 to 1.01) — not significant
Repeated elsewhere
Partially Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The trial is widely cited as positive on the strength of its subgroup and its secondary radiographic endpoint. The declared primary endpoint in the whole randomised population was not met.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, including a 70 mg effervescent formulation
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Hip density -2.4% (95% CI -2.9 to -1.8) on stopping, P<0.001; nonvertebral fracture RR 1.00 (0.76 to 1.32)
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The primary endpoint was a bone-density measurement, and fracture was exploratory. A reader looking for whether ten years beats five on fracture is reading an underpowered secondary analysis.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, including a 70 mg effervescent formulation
Interval reported. 95% CI -2
Written into the record, not signed off as a reviewed claim.
Pooled secondary analysis of FIT, FLEX and HORIZON-PFT for atypical femur fracture (Black 2010)
How many people
14195
Study design
Secondary analysis of three randomised trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
12 fractures in 10 patients, 2.3 per 10,000 patient-years; alendronate relative hazard 1.03 (95% CI 0.06 to 16.46)
Repeated elsewhere
Failed to Replicate
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The authors state the analysis was underpowered for definitive conclusions. A confidence interval running from 0.06 to 16.46 excludes essentially nothing, and this result was frequently reported as reassurance.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, including a 70 mg effervescent formulation
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Alendronic acid
What a person takes: Oral tablet, including a 70 mg effervescent formulation.
The measurement behind this step
Taken fasting with plain water and with the patient upright afterwards, because absorption is negligible with food and the molecule is directly irritant to the oesophagus if it lodges there. The effervescent tablet exists to reduce that second problem by delivering the drug already in solution.
Getting in
Swallowed, and almost entirely not absorbed
The tablet has to be taken on an empty stomach because food destroys its absorption completely. Even under the best conditions only about half of one percent gets into the blood.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The geminal bisphosphonate carries two phosphonate groups and an amine, giving it a high charge at gut pH and negligible passive permeability. Mean oral bioavailability is 0.64% fasting and negligible with food; divalent cations in dairy, coffee and juice chelate the drug in the lumen, cutting absorption a further 60%.
The fraction that gets in goes straight to bone mineral
What reaches the blood does not circulate for long. Roughly half is passed in urine and the rest sticks to bone, where it stays for years.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The P-C-P backbone chelates calcium in hydroxyapatite with high affinity, so plasma concentrations after therapeutic oral doses stay below 5 ng/mL, too low for routine analytical detection. Steady-state volume of distribution excluding bone is at least 28 L. The terminal half-life exceeds ten years, reflecting slow release from the skeleton rather than slow clearance from plasma.
It concentrates exactly where bone is being dissolved
The drug binds hardest to freshly exposed mineral, which is where the demolition cells are working. That is why it accumulates under those cells rather than spreading evenly.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Radiolabelled alendronate showed roughly 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces in mice. Under a resorbing osteoclast the sealing zone maintains a pH near 4.5, which liberates bound drug from the mineral into a small, very high local concentration.
The cell swallows the drug along with the mineral it is dissolving
The demolition cell cannot take the mineral apart without taking the drug in with it. It poisons itself by doing its own job.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Liberated bisphosphonate enters the osteoclast by fluid-phase endocytosis of the resorption lacuna contents, then escapes the endosome into the cytosol. Uptake is therefore proportional to resorptive activity, which is the pharmacological reason the drug is selective for the cell type it acts on without any targeting ligand.
Inside, it blocks the enzyme that makes the cell’s lipid anchors
The cell needs a particular chemical tag to attach several of its own control proteins to its inner membrane. The drug blocks the enzyme that makes that tag, and the control proteins stop working.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Alendronate inhibits farnesyl diphosphate synthase with an IC50 of 460 nM, depleting farnesyl and geranylgeranyl diphosphate. Small GTPases including Rab, Rho and Rac lose their prenyl anchors and cannot localise to membrane, so vesicle trafficking and cytoskeletal control fail. The osteoclast still attaches to bone but loses its ruffled border, the folded membrane through which acid and protease are secreted.
Demolition slows, building continues, and fewer bones break
With the demolition side suppressed, the building side keeps filling in and density rises. The point of that is fewer fractures, and in women who had already fractured, fractures roughly halved.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Resorption falls with no direct effect on formation, though formation eventually declines too because the two are coupled through the remodelling cycle. Histomorphometry in baboons and rats shows fewer remodelling sites with formation exceeding resorption at those remaining. The clinical translation is a 47% reduction in new morphometric vertebral fracture over three years in women with a prior vertebral fracture, and no significant clinical-fracture reduction in women without one.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Postmenopausal women with osteoporosis, men with osteoporosis, people taking long-term glucocorticoids, and people with Paget disease of bone.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Alendronate sodium is not indicated for use in pediatric patients.”
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
On older people, the label states: “Of the patients receiving alendronate sodium in the Fracture Intervention Trial (FIT), 71% (n=2302) were greater than or equal to 65 years of age and 17% (n=550) were greater than or equal to 75 years of age.”
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Available data on the use of alendronate sodium in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes.”
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary It is not known whether alendronate is present in human breast milk, affects human milk production, or has effects on the breastfed infant.”
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
On people with reduced liver function, the label states: “As there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment.”
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
On people with reduced kidney function, the label states: “Alendronate sodium is not recommended for patients with creatinine clearance less than 35 mL/min .”
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
Where the result stopped carrying
The primary-prevention arm of the pivotal trial missed its primary endpoint: clinical fracture relative hazard 0.86 (95% CI 0.73 to 1.01) in 4432 women
In women whose femoral-neck density was above the osteoporotic threshold there was no reduction at all, relative hazard 1.08 (0.87 to 1.35)
Osteonecrosis of the jaw and atypical femoral fracture were both found after approval by clinicians reporting cases, not by the registration programme
FLEX could not answer the duration question it was run to answer, because it was powered for bone density and treated fracture as exploratory
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet, including a 70 mg effervescent formulation
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Taken fasting with plain water and with the patient upright afterwards, because absorption is negligible with food and the molecule is directly irritant to the oesophagus if it lodges there. The effervescent tablet exists to reduce that second problem by delivering the drug already in solution.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
No boxed warning. Oesophagitis, oesophageal ulceration and erosion are the characteristic label warnings and drove the administration requirements. Osteonecrosis of the jaw and atypical subtrochanteric or diaphyseal femoral fracture are class warnings established after approval; the Swedish national estimate of the excess atypical fracture rate is about 5 cases per 10,000 patient-years, duration-dependent, and falling 70% per year after the drug is stopped. In FIT there was no significant difference between groups in adverse experiences, including upper gastrointestinal disorders.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, including a 70 mg effervescent formulation
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The effervescent tablet exists to reduce that second problem by delivering the drug already in solution.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
56 products list this as an active ingredient in the United States drug directory. 52 of them contain it and nothing else.
FDA National Drug Code directory · 13371-111 · read 2026-08-29
They are sold as powder, solution, tablet and tablet, effervescent, taken oral.
FDA National Drug Code directory · 13371-111 · read 2026-08-29
The regulator's established pharmacologic class for it is bisphosphonate [epc] and diphosphonates [cs].
FDA National Drug Code directory · 13371-111 · read 2026-08-29
23 published labels name it as an active ingredient. 22 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-29
ALENDRONATE SODIUM is oral at 3 DOSAGE FORMS AND STRENGTHS Tablets: 5 mg, 10 mg, 35 mg, 40 mg and 70 mg ( 3 ) Alendronate Sodium Tablets, USP 5 mg are white, circular, biconvex tablets debossed with 'C234' on one side and plain on the other side., recorded as fda label in effect 2023-08-25 in the United States.
US prescribing information · 91a0f73a-d8cd-4197-b431-40707a2150b9 · read 2026-08-30
Recorded price in US: 0.11624–0.28421 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 19 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Alendronic acid studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the fracture benefit shown in women with a prior vertebral fracture transfers to women with only low bone density — the primary endpoint in that population was not met
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That continuing beyond five years is better than stopping, when the one randomised comparison found identical nonvertebral fracture rates
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a rise in bone mineral density on a scan is itself the benefit, rather than a surrogate for the fracture that did or did not happen
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the randomised trials ruled out atypical femoral fracture, when the pooled analysis says in its own conclusion that it was underpowered
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Alendronic acid are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
In women who had already fractured a vertebra, it halved the next one
In plain words
Two thousand women who had already broken a bone in their spine were given the drug or a dummy tablet for three years. Eight in a hundred on the drug had a new spinal fracture on x-ray, against fifteen in a hundred on the dummy.
What was measured
New morphometric vertebral fracture at 36 months, 8.0% against 15.0%, RR 0.53 (95% CI 0.41 to 0.68)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Fracture Intervention Trial vertebral-fracture arm randomised 2027 women aged 55 to 81 with low femoral-neck bone density and at least one existing vertebral fracture to placebo (1005) or alendronate (1022) for 36 months. New morphometric vertebral fracture, the primary endpoint, occurred in 78 (8.0%) on alendronate against 145 (15.0%) on placebo, relative risk 0.53 (95% CI 0.41 to 0.68). Clinically apparent vertebral fractures were 2.3% against 5.0%, relative hazard 0.45 (0.27 to 0.72). Any clinical fracture, the main secondary endpoint, was 13.6% against 18.2%, relative hazard 0.72 (0.58 to 0.90). Hip fracture relative hazard was 0.49 (0.23 to 0.99) and wrist 0.52 (0.31 to 0.87). Follow-up radiographs were obtained for 98% of surviving participants.
Written into the record, not signed off as a reviewed claim
In women who had not yet fractured, the trial missed its primary endpoint
In plain words
The other half of the same trial enrolled women with thin bones but no spinal fracture. Over four years it did not significantly reduce the fractures that actually present to a doctor. It worked only in the subgroup whose hip density was already in the osteoporotic range.
What was measured
Clinical fracture over 4.2 years, relative hazard 0.86 (95% CI 0.73 to 1.01) — confidence interval crosses 1
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The Fracture Intervention Trial clinical-fracture arm randomised 4432 women aged 54 to 81 with femoral-neck bone mineral density of 0.68 g/cm2 or less and no vertebral fracture, for an average of 4.2 years. Clinical fractures fell from 312 to 272 events, a 14% reduction that did not reach significance: relative hazard 0.86 (95% CI 0.73 to 1.01). In the prespecified subgroup with femoral-neck T-score below -2.5, the reduction was 36% (RH 0.64, 95% CI 0.50 to 0.82, number needed to treat 15); in women with higher density there was no reduction at all (RH 1.08, 95% CI 0.87 to 1.35). Radiographic vertebral fracture, a secondary endpoint, did fall by 44% (RR 0.56, 95% CI 0.39 to 0.80), with a number needed to treat of 60.
Written into the record, not signed off as a reviewed claim
The enzyme it inhibits was identified, and it is not the obvious one
In plain words
For years the drug was described as simply poisoning the demolition cells. The specific enzyme was pinned down in 2000, and it sits in the same chemical pathway that statins act on, several steps further along.
What was measured
IC50 460 nM against recombinant human farnesyl diphosphate synthase; no inhibition of IPP isomerase or GGPP synthase
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Bergstrom and colleagues narrowed the candidate targets by HPLC analysis of products from liver cytosolic extract and then tested each recombinant enzyme. Alendronate inhibited recombinant human farnesyl diphosphate synthase with an IC50 of 460 nM, and the liver extract activity at 1700 nM. It did not inhibit isopentenyl diphosphate isomerase or geranylgeranyl diphosphate synthase at all. Pamidronate gave 500 nM and risedronate 3.9 nM on the same enzyme; etidronate was negligible at 80 micromolar and clodronate inactive, which is the structural evidence that non-nitrogen bisphosphonates work by a different mechanism entirely. In purified osteoclasts alendronate inhibited incorporation of tritiated mevalonolactone into 18-25 kDa proteins, the small GTPase band.
Written into the record, not signed off as a reviewed claim
Ten years of treatment has never been shown to beat five
In plain words
Women who had taken the drug for five years were randomly assigned to keep going or to switch to a dummy tablet. Over the next five years the two groups broke the same number of bones outside the spine. Only the fractures that hurt in the spine were fewer on continued treatment.
What was measured
That longer treatment is better treatment — a bone-density argument that the only randomised comparison of five against ten years does not support outside clinical vertebral fracture
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
FLEX randomised 1099 women with a mean of five years of prior alendronate to a further five years of alendronate (5 mg/d, n=329, or 10 mg/d, n=333) or to placebo (n=437). Total hip bone density, the primary endpoint, fell 2.4% (95% CI -2.9 to -1.8) in those who stopped, but stayed at or above pretreatment levels of ten years earlier. Cumulative nonvertebral fracture risk was identical: 19% against 18.9%, RR 1.00 (95% CI 0.76 to 1.32). Clinically recognised vertebral fractures were lower on continued treatment, 2.4% against 5.3%, RR 0.45 (0.24 to 0.85), but morphometric vertebral fractures were not, 9.8% against 11.3%, RR 0.86 (0.60 to 1.22). Fracture was an exploratory outcome, not the primary one, so the trial was not designed to answer this question.
Written into the record, not signed off as a reviewed claim
Atypical femur fracture: from case reports, to an underpowered null, to a real risk
In plain words
Surgeons began reporting an unusual thigh-bone fracture in long-term users. A re-analysis of the big randomised trials found the event was far too rare for those trials to settle the question. A Swedish national study of every femoral fracture in a year then showed the association is real, and small.
What was measured
That the randomised trials had ruled the risk out — they had not, they were underpowered, and the confidence intervals ran from 0.06 to 16.46
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Black and colleagues reviewed 284 hip or femur fracture records among 14,195 women in FIT, FLEX and HORIZON-PFT and classified 12 fractures in 10 patients as subtrochanteric or diaphyseal, a combined rate of 2.3 per 10,000 patient-years. Relative hazards were 1.03 (95% CI 0.06 to 16.46) for alendronate in FIT, 1.33 (0.12 to 14.67) for continued alendronate in FLEX and 1.50 (0.25 to 9.00) for zoledronic acid in HORIZON-PFT. The authors state the study was underpowered for definitive conclusions, and the confidence intervals make that unarguable. Schilcher and colleagues then reviewed radiographs of 1234 of the 1271 Swedish women aged 55 or over with a subtrochanteric or shaft fracture in 2008, identified 59 atypical fractures, and found an age-adjusted relative risk of 47.3 (95% CI 25.6 to 87.3) with an absolute increase of 5 cases per 10,000 patient-years. Risk rose with duration (odds ratio 1.3 per 100 daily doses) and fell by 70% per year after withdrawal.
Written into the record, not signed off as a reviewed claim
The label states that nobody knows how long to take it
In plain words
The prescribing information carries a limitation of use saying the optimal duration has not been determined, and suggests considering stopping after three to five years in people at low risk. That is a regulator conceding an open question, not a recommendation.
What was measured
That there is a known correct treatment duration — the label explicitly says there is not, and the only randomised duration comparison was powered for bone density rather than fracture
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The current United States label carries the limitation "Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use." This sits on top of a drug whose terminal half-life is estimated to exceed ten years, reflecting slow release from the skeleton, and which after ten years of daily treatment is releasing from bone about 25% of the amount being absorbed. A drug that keeps acting after it is stopped makes duration a different question from that for a drug cleared in a day, and no randomised trial has compared stopping points other than the five-against-ten comparison in FLEX.
Source
Alendronate sodium United States prescribing information, Indications and Usage (Limitations of Use) and Clinical Pharmacology 12.3 (openFDA label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Almost none of a swallowed tablet is absorbed, and food abolishes it
In plain words
About six-tenths of one percent of the tablet reaches the bloodstream, and only if the stomach is empty. Taken with breakfast, or up to two hours after it, essentially none is absorbed. Coffee or orange juice cuts absorption by about 60%.
What was measured
Mean oral bioavailability 0.64% fasting in women, 0.59% in men; negligible when taken with or within two hours after food
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mean oral bioavailability relative to intravenous dosing is 0.64% in women across 5 to 70 mg doses after an overnight fast and two hours before breakfast, and 0.59% in men. Bioavailability is negligible when the drug is given with or up to two hours after a standardised breakfast, is reduced approximately 60% by coffee or orange juice, and is reduced approximately 50% when given 15 minutes rather than four hours before a meal. Protein binding is about 78%, there is no evidence of metabolism in animals or humans, and roughly 50% of an intravenous dose is excreted unchanged in urine within 72 hours.
Source
Alendronate sodium United States prescribing information, Clinical Pharmacology 12.3 (openFDA label endpoint)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
22 documents were read for this substance.
RNAWiki source record
22 of them state the same bioavailability, and they agree.
RNAWiki source record
22 of them state the same proteinBinding, and they agree.
RNAWiki source record
22 of them state the same volumeOfDistribution, and they agree.
RNAWiki source record
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No register row and no identity class settled the question.
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What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
20 approved applications cover products containing this substance. The earliest was NDA020560, approved 19950929 to ORGANON.
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What is not here
7 questions this page could not answer
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What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A mineral-seeking molecule that osteoclasts swallow while dissolving bone and that shuts down the enzyme they need to keep working — in 2027 women who already had a spinal fracture it cut new radiographic spinal fractures from 15.0% to 8.0% over three years and hip fractures by about half, but in 4432 women without a prior spinal fracture the same trial missed its primary endpoint, reducing clinical fractures only from 312 to 272 events.
Recorded evidence blocks (8)
Q1
On the Alendronic acid label: indicated for what?
"Alendronate sodium is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women ( 1.1 , 1.2 ) Treatment to increase bone mass in men with osteoporosis ( 1.3 ) Treatment of glucocorticoid-induced osteoporosis ( 1.4 ) Treatment of Paget's disease of bone ( 1.5 ) Limitations of use…": indications and usage on Alendronic acid's label. DailyMed label · c7e470d6-508e-466e-a78d-060bbbc9745c · 2026-07-03
Q2
129 registered trials of Alendronic acid — at which phases?
Registered studies posting no result
90 of 129
129 registered studies of Alendronic acid: 38 phase2, 35 phase3, 35 phase4, 12 na, 8 na or unstated, 8 phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
797 with a PubMed record
Show the evidence
phase2
38
phase3
35
phase4
35
na
12
na or unstated
8
phase1
8
7 more recorded rows
completed
91
terminated
13
unknown
13
active not recruiting
4
recruiting
4
withdrawn
3
enrolling by invitation
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
11 of Alendronic acid's trials stopped: futility/efficacy, accrual/recruitment, funding/business, other?
futility/efficacy (1), accrual/recruitment (6), funding/business (1) and other (3): Alendronic acid's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Slow accrual than anticipated."; 11 of 129 registered studies
Show the evidence
Trial
NCT00236002
terminated; "Slow accrual than anticipated."
NCT00359385
withdrawn; "incomplete enrollment"
NCT00471237
terminated; "Terminated for futility by sponsor after a pre-planned interim review of data"
NCT00572299
terminated; "Terminated due to recruitment problems"
NCT00713258
terminated; "Slow enrolment"
NCT00822029
terminated; "only 2 patients inclued and Study Principal Investigator has left the hospital"
5 further recorded trials
NCT01131884
terminated; "Only 1 participant enrolled since the beginning of this study"
NCT01512446
terminated; "low recruitment rate"
NCT01656629
terminated; "Inability to analyze collected samples due to no funds."
NCT02322099
terminated; "Due to the COVID-19 pandemic the study was terminated prematurely"
NCT06973109
withdrawn; "Investigator left the institution"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Alendronic acid used Alendronate 70 mg tablets — over how long?
Human studies of Alendronic acid used "Alendronate 70 mg tablets". ClinicalTrials.gov · 2026-09-01
11 recorded entries; human; also "Alendronate Sodium Tablets 70mg", "Fosamax® Tablets 70mg", "Alendronate Sodium Tablets, 10 mg"
Show the evidence
human
NCT00404820
Alendronate 70 mg tablets
NCT00835406
Alendronate Sodium Tablets 70mg
NCT00835406
Fosamax® Tablets 70mg
NCT00983996
Alendronate Sodium Tablets, 10 mg
NCT00983996
Fosamax Tablets, 10 mg
NCT01012934
Alendronate Sodium Tablets, 70 mg
5 more recorded rows
humanNCT01012934
Fosamax Tablets, 70 mg
humanNCT01133496
Fosamax Tablets 70 mg
humanNCT03435094
Binosto 70Mg Effervescent Tablet
humanNCT03435094
Fosamax 70Mg Tablet
humanNCT03980847
Alendronate 20 mg
recorded 2026-09-01 · last checked 2026-09-04
Q5
Which 56 trials of Alendronic acid posted no result?
Posted no result
56 of 56 completed trials
Registrations
NCT00000412, NCT00983996, NCT01012934, NCT00004488, NCT00004489 and NCT00480662, and 50 more
Completion dates
oldest 2002-04; newest 2024-06-21
Show the evidence
Trial
NCT00000412
2002-04
NCT00983996
2002-07
NCT01012934
2002-08
NCT00004488
2002-09
NCT00004489
2002-09
NCT00480662
2002-10
14 further recorded trials
NCT02416271
2003-05
NCT00001720
2003-06
NCT00577850
2004-02
NCT00092014
2004-04-01
NCT00936260
2004-12
NCT02598440
2005-05
NCT00000427
2005-10
NCT00048841
2005-12
NCT00177619
2005-12
NCT00000400
2006-06
NCT00277251
2006-06
NCT00157690
2006-08
NCT00061256
2006-09
NCT00005006
2006-12
Q6
At the median, Alendronic acid's trials enrolled 81.5 people — anything larger?
Median enrolment
81.5
Largest enrolment
684815
Registered trials counted
128
Q7
What do 27848 spontaneous reports say about Alendronic acid — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Alendronic acid appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 27848 reaction mentions were counted: femur fracture 4152; pain 3480; fatigue 2791; abdominal discomfort 2674. FAERS via Open Targets · CHEMBL675 · 2026-06-24
Show the evidence
femur fracture
4152
pain
3480
fatigue
2791
abdominal discomfort
2674
alopecia
2657
fall
2555
4 more recorded rows
systemic lupus erythematosus
2432
pemphigus
2397
rheumatoid arthritis
2377
arthralgia
2333
recorded 2026-06-24 · last checked 2026-09-04
Q8
Which 10 reactions does Alendronic acid's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
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✓ source coverage passed: 6 source rows
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