What are the treatment recommendations for osteoporosis in smokers?

From the Guidelines

Smokers with osteoporosis should be treated with a combination of smoking cessation and standard osteoporosis therapies, including first-line medications such as bisphosphonates, to reduce the risk of fractures and improve quality of life. The most recent and highest quality study, published in 2024 1, recommends that men at a high risk of fracture should be treated with oral bisphosphonates, such as alendronate or risedronate, as first-line treatment. Additionally, the study suggests that denosumab or zoledronate can be used as second-line treatments for men at a high risk of fracture.

Some key points to consider in the treatment of osteoporosis in smokers include:

• Ensuring vitamin D and calcium repletion, with a strong recommendation for men above the age of 65 years to ensure adequate vitamin D and calcium intake 1
• Using oral bisphosphonates as first-line treatment for men at a high risk of fracture, with a strong recommendation for alendronate or risedronate 1
• Considering denosumab or zoledronate as second-line treatments for men at a high risk of fracture, with a strong recommendation 1
• Recommending physical exercise and a balanced diet to all men with osteoporosis, with a strong recommendation 1
• Assessing serum total testosterone as part of the pre-treatment assessment of men with osteoporosis, with a weak recommendation 1

It is also important to note that smoking cessation is a crucial component of osteoporosis treatment in smokers, as smoking accelerates bone loss and reduces the effectiveness of osteoporosis treatments. The American College of Physicians guideline update from 2017 1 recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis, with a strong recommendation and high-quality evidence.

In terms of specific medications and dosages, the following may be considered:

• Alendronate (70mg once weekly)
• Risedronate (35mg once weekly)
• Zoledronic acid (5mg IV annually)
• Denosumab (60mg subcutaneously every 6 months)
• Teriparatide (20mcg subcutaneously daily for up to 24 months)
• Calcium supplements (1000-1200mg daily)
• Vitamin D (800-1000 IU daily)

Regular bone mineral density testing every 1-2 years is also important to monitor treatment effectiveness, with more frequent monitoring often needed for smokers due to their accelerated bone loss. Overall, a comprehensive treatment plan that includes smoking cessation, standard osteoporosis therapies, and regular monitoring can help to reduce the risk of fractures and improve quality of life for smokers with osteoporosis.

From the FDA Drug Label

Instruct patients to take supplemental calcium and vitamin D, if daily dietary intake is inadequate. Weight-bearing exercise should be considered along with the modification of certain behavioral factors, such as cigarette smoking and/or excessive alcohol consumption, if these factors exist. The treatment recommendations for osteoporosis in smokers include:

• Supplemental calcium and vitamin D to ensure adequate daily intake
• Weight-bearing exercise
• Modification of behavioral factors, such as:
  • Cessation of cigarette smoking
  • Reduction of excessive alcohol consumption 2

From the Research

Pathophysiology of Smoking and Osteoporosis

• Smoking is thought to be a risk factor for osteoporosis development, and it can negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur 3.
• Bone mineral density was significantly lower in smokers than in non-smokers, and current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers 4, 3.
• Smoking cessation can increase levels of osteocalcin and uncarboxylated osteocalcin in human sera, which are bone formation markers, and can rescue bone homeostasis 4.

Treatment Recommendations for Osteoporosis in Smokers

• Bisphosphonates, such as alendronate and risedronate, are safe and effective agents for the treatment and prevention of osteoporosis, and they can increase bone mass and reduce the risk of vertebral fractures 5.
• Combining a bisphosphonate with estrogen can produce greater gains in bone mass compared with either agent used alone, but it is not clear whether there is a greater benefit of combination therapy on fracture risk 5.
• Transitioning from alendronate or risedronate to other therapies, such as zoledronic acid, strontium ranelate, denosumab, or teriparatide, can be considered for patients who do not respond adequately to bisphosphonates, and it can maintain therapeutic effects or cause further increases in bone mineral density 6.
• Oral bisphosphonate therapies, such as alendronate, ibandronate, and risedronate, can have different effects on the central and peripheral skeleton, and ibandronate and alendronate may have greater effects on the spine than risedronate 7.