Osteoporosis: Sequential Therapy and Lifelong Maintenance

V Krishnamurthy MD, DM, FRCP (London)
CEO & Consultant Rheumatologist, Chennai Meenakshi Multispecialty Hospital, Chennai
Consultant Rheumatologist, Apollo Specialty Hospitals, Chennai

Osteoporosis, though a common problem affecting adults, it is not well studied or documented in Indian patients. Management is done by health care providers of different specialities. It would be better if it is done based on data driven scientific principles. Though there are several medications available in the international arena, only five drugs (teriparatide, denosumab, alendronate, risedronate & ibandronate) are important for the management of osteoporosis in India. Good knowledge about these molecules can certainly save patients from crippling osteoporotic fractures.

My preferred regime of therapy

The rule of thumb is, if a patient has got only osteopenia, supplementation with calcium and vitamin D is sufficient.  Correction of vitamin D is important, and the patient is advised to have regular exercise and exposure to sunlight. In the case of osteoporosis without fracture in adults, they can be started on bisphosphonates with calcium + vitamin D supplements. This also applies to those who are on steroids. In patients who do not tolerate oral bisphosphonates like alendronate or risedronate or when patient compliance is questionable, it is better to opt for once-a-year zoledronic acid infusion. In some, ibandronate once a month orally is also successful. In those with the history of fracture or recent fracture of bones and osteoporosis, it is better to start an anabolic agent like teriparatide initially for 6-18 months followed by either bisphosphonates or denosumab. In patients who are averse to daily injections, either bisphosphonates or denosumab can be started. A disadvantage of anabolic agents and denosumab is the cost factor and parenteral application.

Experience with sequential or combination therapy

In my practice I find sequential therapy more effective than a combination therapy. The preferred sequential therapy is teriparatide for 12- 18 months followed by either risedronate or denosumab for three years. Combination therapy can be reserved for very severe cases with extensive fractures and a poor response to sequential therapy. With informed consent we can combine teriparatide with denosumab or alendronate.

Experience with treatment withdrawal

Patients do well with maintenance therapy of bisphosphonates or denosumab. If they are on denosumab, there is always a transition plan, since withdrawal of denosumab causes loss of BMD. It is then followed by an oral or parenteral bisphosphonate.  When the patient doctor rapport is good, the follow-up is well maintained including the drug holiday. Ideal drug holidays are five years of alendronate followed by two years of drug holiday. Zoledronic acid can have a three-year drug holiday and risedronate one year. In a few patients, withdrawal of bisphosphonates following a drug holiday did not cause any adverse impact. Some may sustain a fracture despite a good maintenance therapy, requiring change in management strategy. Assessing bone turnover markers is important at this juncture. The occurrence of atypical femoral fractures or osteonecrosis of jaw are very rare, and I have seen only one case of atypical fracture with bisphosphonates.

Lifestyle advices

Lifestyle advice is important. All patients with osteoporosis should be educated regarding the importance of exercise, cessation of smoking, reducing or abstinence of alcohol, adequate sunlight exposure, vision correction, core muscle strengthening, neurological assessment and reducing sedatives. Interacting with other health care providers of the patient may ensure an ideal prescription.

Suggested reading

  1. Reid IR &Billington EO. Drug therapy for osteoporosis in older adults. Lancet 2022; 399:1080-92
  2. Le Boff MS et al. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis Int 2022; 33:2049-2102