Fosamax (Alendronate) for Women 65 and Older: What Changes as You Age

Why Alendronate Matters More, Not Less, After 65

Bone loss does not plateau after menopause. The rate of trabecular bone loss accelerates again in the late 60s and into the 70s, partly because estrogen decline is now compounded by age-related decreases in calcium absorption, vitamin D activation, and physical activity. Bone turnover markers rise again in many women after age 65, even if they were stable for years.

The consequence is real. Women over 65 account for the large majority of osteoporotic hip fractures, and the one-year mortality after hip fracture in this age group is approximately 24 percent. Alendronate, a nitrogen-containing bisphosphonate, works by binding to hydroxyapatite in bone and inhibiting osteoclast-mediated resorption. It does not become less effective simply because you are older. What changes is the clinical context around the drug.

The Fracture Intervention Trial: The Evidence Base for Older Women

The Fracture Intervention Trial (FIT) remains the foundational dataset for alendronate in postmenopausal women. In the vertebral fracture arm of FIT, women with a prior vertebral fracture and low bone mineral density (BMD) who received alendronate for three years had a 51 percent reduction in hip fracture risk and a 47 percent reduction in new vertebral fractures compared with placebo. Mean participant age was 71. This is not a trial extrapolated to older women. Older women were the trial.

The FIT long-term extension, FLEX, followed women for an additional five years (ten years total) and found that those who continued alendronate maintained BMD gains and had significantly fewer clinical vertebral fractures compared with those who switched to placebo, though the nonvertebral and hip fracture difference did not reach statistical significance in the overall FLEX cohort.

How Post-Menopause Biology Shapes the Drug's Behavior

Alendronate's pharmacokinetics do not change dramatically with age alone. Oral bioavailability is already very low (approximately 0.7 percent under fasting conditions), so the dominant determinant of systemic exposure is renal clearance. Because GFR declines with age, a woman who had a GFR of 75 mL/min at 55 may have a GFR of 48 mL/min at 70. Alendronate is not metabolized; it is either absorbed into bone or excreted unchanged by the kidneys. Reduced renal clearance means more circulating drug before skeletal uptake, raising the theoretical risk of renal tubular toxicity at GFR levels below 35 mL/min/1.73 m².

The FDA-approved labeling recommends against use if creatinine clearance is below 35 mL/min. Check renal function before initiating and annually thereafter.

Reassessing Risk at 65 and Beyond

When a woman turns 65, or when she transitions from a general adult medicine provider to a geriatric specialist or a new women's-health clinician, her fracture risk needs a fresh calculation, not just a carry-forward from her previous chart.

FRAX After 65: What Changes

FRAX, the WHO fracture risk assessment tool, incorporates age as a continuous variable, so a woman's 10-year probability of major osteoporotic fracture rises substantially from her mid-60s to her mid-70s even if her T-score is unchanged. A woman with a T-score of -2.2 at age 62 may have been below the treatment threshold at that point. By age 68, the same T-score produces a FRAX probability that crosses the threshold recommended by the National Osteoporosis Foundation / American College of Rheumatology, and treatment becomes appropriate.

Recalculate FRAX at each major transition point: at initial geriatric assessment, after any fracture, and after significant weight change or new corticosteroid use.

Secondary Causes That Emerge or Worsen After 65

Before attributing fracture risk to postmenopausal bone loss alone, screen for secondary causes that become more prevalent with age.

• Vitamin D deficiency (serum 25-OH-D below 20 ng/mL affects roughly 35 percent of women over 60)
• Primary hyperparathyroidism, which peaks in postmenopausal women
• Subclinical hyperthyroidism or overtreatment with levothyroxine
• Malabsorption from celiac disease, gastric bypass, or inflammatory bowel disease
• Long-term glucocorticoid use, which is common in women managing autoimmune conditions

Alendronate does not address any of these root causes. If you start it without correcting vitamin D deficiency, for example, you risk hypocalcemia and diminished drug effect.

Dosing, Administration, and What Actually Goes Wrong at This Life Stage

The standard oral dose is 70 mg once weekly, taken on the same day each week, first thing in the morning, with a full 8-oz (240 mL) glass of plain water, at least 30 minutes before any food, drink, or other medication. You remain upright (sitting or standing) for at least 30 minutes afterward.

This seems straightforward. In women over 65, it is where things reliably break down.

Swallowing and Esophageal Concerns

Dysphagia is more common after 65 due to reduced esophageal motility, hiatal hernia, and previous esophageal damage. Alendronate causes direct esophageal mucosal irritation if it sits in contact with the mucosa rather than passing quickly to the stomach. Esophageal ulceration and, rarely, esophageal stricture have been reported. If you have active esophageal disease, difficulty swallowing, or cannot remain upright for 30 minutes (for example, due to spinal deformity, severe GERD, or functional limitations), oral weekly alendronate is not the right formulation for you.

An intravenous bisphosphonate such as zoledronic acid (Reclast, 5 mg IV once yearly) bypasses the GI route entirely and may be a better fit. Zoledronic acid reduced hip fracture risk by 41 percent in the HORIZON Key Fracture Trial, with a participant mean age of 73.

Memory, Routine, and Adherence

Adherence to weekly oral bisphosphonates drops substantially over time. In real-world data, fewer than 50 percent of women remain on oral bisphosphonate therapy at one year, and non-adherence erodes fracture protection. If cognitive changes or complex medication schedules make weekly dosing unreliable, switching to an annual IV infusion or a quarterly subcutaneous injection (denosumab) may preserve the fracture-reduction benefit more reliably.

Drug Interactions That Pile Up After 65

Polypharmacy is the norm, not the exception, in women over 65. Alendronate's absorption is essentially eliminated by calcium supplements, antacids, and most other oral medications taken within 30 minutes of the dose. The 30-minute separation rule is not a mild suggestion. It is pharmacokinetically mandatory. Common culprits:

• Calcium carbonate taken at breakfast
• Proton pump inhibitors (which also, at high doses, may modestly impair calcium absorption)
• Iron supplements
• Magnesium-containing laxatives

Review the full medication list at every geriatric transition appointment, not just the osteoporosis medications.

The Drug Holiday Decision: Stopping or Continuing After 5 to 10 Years

One of the most common and most misunderstood conversations at the geriatric transition is whether to take a "drug holiday." Bisphosphonates bind to bone mineral and continue to suppress resorption for months to years after the last dose, a property that makes a planned break possible for lower-risk women.

The WomanRx framework for making this decision at age 65 and beyond organizes patients into three groups based on FLEX data and current guideline synthesis:

Group 1: Continue without a holiday (highest risk)

• Prior hip or vertebral fracture
• T-score below -2.5 at the hip after 5 years of treatment
• Ongoing high-dose glucocorticoid use
• Multiple FRAX risk factors (age over 70, smoking, fall history, low body weight)

Group 2: Holiday after 5 years, reassess at 2-3 years (lower risk)

• No prior fracture
• T-score at or above -2.5 at the hip after 5 years
• No new major risk factors

Group 3: Reassess rather than automatically continue (moderate risk)

• Prior vertebral fracture only (no hip fracture)
• T-score between -2.0 and -2.5 after 5 years
• FRAX 10-year major fracture probability below 20 percent

The American Society for Bone and Mineral Research (ASBMR) 2016 Task Force recommends that after a 5-year drug holiday, women be reassessed with DXA and clinical risk factors. If BMD has declined significantly or a fracture has occurred during the holiday, restarting therapy is appropriate.

A drug holiday is not a permanent stop. It is a scheduled pause with a plan. A woman who stops alendronate at 68 with no reassessment plan may be at 73 with a hip fracture and no record of why her treatment was discontinued.

Falls, Frailty, and the Fracture Equation

Bone density explains only part of fracture risk in older women. Falls account for a large share of the clinical equation. A woman with osteopenia who falls repeatedly has a higher absolute fracture risk than a woman with osteoporosis who never falls.

The U.S. Preventive Services Task Force recommends exercise interventions for community-dwelling adults over 65 at increased fall risk. At geriatric transition appointments, assess:

• Gait speed and balance (Timed Up and Go test)
• Visual acuity
• Medications that increase fall risk: benzodiazepines, anticholinergics, antihypertensives causing orthostatic hypotension, sleep aids
• Home safety: rugs, lighting, bathroom grab bars

Alendronate does not prevent falls. It makes the bones you land on more resistant to breaking. Both sides of that equation matter.

Rare but Serious Risks That Require Monitoring

Atypical Femoral Fractures

Atypical femoral fractures (AFF) are low-energy, subtrochanteric or diaphyseal femur fractures associated with long-term bisphosphonate use. They are rare. The absolute risk is approximately 3.2 to 50 cases per 100,000 person-years, increasing with duration of use beyond 5 years. The fracture risk prevented by alendronate in high-risk women vastly exceeds the AFF risk for most women. But the signal matters, and older women on long-term therapy should be asked at every visit whether they have prodromal thigh or groin pain, which often precedes AFF by weeks to months.

If prodromal pain is present, stop the drug and get bilateral femur X-rays. Bilateral presentation is common.

Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) with oral bisphosphonates at osteoporosis doses is rare, with a risk estimated at 1 in 10,000 to 1 in 100,000 patient-years in patients receiving oral bisphosphonates for osteoporosis, far lower than in patients receiving high-dose IV bisphosphonates for cancer. Risk rises with invasive dental procedures, poor oral hygiene, and immunosuppression, all more common in older women.

Before starting alendronate, complete any necessary dental work. Maintain routine dental care throughout therapy. There is no evidence that stopping alendronate before routine dental procedures reduces ONJ risk in osteoporosis-dose patients, and AAOMS guidelines no longer recommend drug holidays for routine dental care in this population.

Hypocalcemia

Hypocalcemia is more clinically significant in older women because it can precipitate cardiac arrhythmias, muscle cramps, and confusion. Before starting alendronate, ensure serum calcium is normal, vitamin D is replete (target 25-OH-D of 30 to 50 ng/mL), and dietary calcium intake is adequate (1,200 mg per day total from food and supplements combined for women over 51, per NIH Office of Dietary Supplements).

Pregnancy and Lactation: Safety Information

Alendronate is FDA Pregnancy Category C / X based on animal data showing fetal harm (incomplete fetal ossification at low doses, increased fetal mortality at higher doses). Human bisphosphonate exposure in pregnancy has been associated with transient neonatal hypocalcemia in case reports.

For a woman over 65, pregnancy is not physiologically possible. This section is included for clinical completeness and for the rare situation of premenopausal women or perimenopausal women in the age 50 to 55 range who may be transitioned to a geriatric or bone health specialist while still at some reproductive potential.

In that context: alendronate should not be used in pregnancy. Bisphosphonates incorporate into the skeleton and persist for years; theoretical fetal exposure through bone resorption during a subsequent pregnancy remains a concern even after drug discontinuation. Women of reproductive age using alendronate should use effective contraception. Lactation data are limited; bisphosphonates bind avidly to bone and have very low serum levels after oral dosing, so breast milk transfer is expected to be minimal, but no formal lactation studies exist in humans.

For any premenopausal woman being considered for alendronate, an individualized risk-benefit discussion with a reproductive endocrinologist or maternal-fetal medicine specialist is appropriate.

Who This Drug Is Right for, and Who Should Reconsider

Right for You If...

• You are a postmenopausal woman with a DXA T-score at or below -2.5 at the hip or spine
• You have a T-score between -1.0 and -2.5 (osteopenia) with a FRAX 10-year hip fracture probability at or above 3 percent or major fracture probability at or above 20 percent, per NOF guidelines
• You have a history of low-trauma fracture after age 50
• Your eGFR is above 35 mL/min/1.73 m²
• You can swallow tablets and remain upright for 30 minutes

Reconsider or Switch Formulation If...

• eGFR is below 35 mL/min/1.73 m² (consider denosumab instead, with monitoring)
• Active esophageal disease, achalasia, or severe GERD despite PPI
• Inability to sit or stand for 30 minutes
• Uncorrected hypocalcemia or severe vitamin D deficiency
• Active invasive dental work planned (delay initiation, not the dental care)
• Prodromal thigh pain on long-term therapy (evaluate for AFF immediately)

"The biggest mistake I see at geriatric transitions is automatic continuation without reassessment," says Rachel Goldberg, MD, WomanRx medical reviewer and women's health specialist. "A woman who was appropriately started on alendronate at 62 may have very different renal function, fracture risk, and medication complexity at 72. The drug may still be exactly right. Or the route, duration, or agent may need to change. You have to actually look."

Monitoring Schedule at 65 and Beyond

Consistent monitoring is what separates good osteoporosis care from prescribing and forgetting.

| Test | Frequency | Notes | |---|---|---| | DXA (hip and spine) | Every 1-2 years initially; every 2-3 years if stable | Compare to baseline; significant loss triggers reassessment | | Serum creatinine / eGFR | Annually | Dose or drug change if eGFR falls below 35 | | Serum calcium and 25-OH vitamin D | Annually | Correct deficiency before and during treatment | | Bone turnover markers (CTX, P1NP) | Optional; 3-6 months after initiation | Confirm suppression of resorption; useful in adherence questions | | Dental evaluation | Before initiation; routine care annually | ONJ surveillance | | FRAX recalculation | At each major transition or after any fracture | Age changes the output even with stable T-score |

After 5 years of therapy, explicitly document whether a drug holiday is planned, rejected with rationale, or deferred pending imaging. This conversation belongs in the chart.

Coordinating the Geriatric Transition: What to Ask and What to Bring

When you move to a new provider, geriatric specialist, or bone health clinic, bring the following to your first visit:

• Your most recent DXA report with T-scores and Z-scores at both hip and spine, and the date
• Your current dose and start date for alendronate
• A complete medication and supplement list, including calcium and vitamin D doses
• Records of any fractures, falls, or bone pain since your last appointment
• Your most recent serum creatinine, calcium, and vitamin D levels

Ask your new clinician directly: "Should we recalculate my FRAX? Is my current bisphosphonate still the best option given my kidneys and my other medications? When should we think about a drug holiday, and what would trigger restarting?"

These are not aggressive or difficult questions. They are the standard of care. A 2022 review in the Journal of Bone and Mineral Research found that provider failure to reassess bisphosphonate duration was one of the leading contributors to inappropriate long-term continuation and to inappropriate early discontinuation, two opposite errors that both increase fracture risk.

The most protective thing you can do after 65 is not simply stay on a medication. It is stay engaged with the evidence around it.