I’ve argued for years that bisphosphonates — the knee-jerk bone drugs recommended for those with osteoporosis regardless of their actual fracture risk — quite often offer no benefit to those who are prescribed them, and for many, do more harm than good. That’s why I was alarmed, but not surprised, by a recent study that found bisphosphonate drugs may be leaving bones weaker — not stronger — at the microscopic level (Ma et al, 2017).
In the study, researchers obtained samples of trabecular bone from three groups of subjects: (1) normal, healthy older adults who had no fractures, (2) individuals who had fractured a bone after at least 1 year of treatment with bisphosphonates, and (3) individuals who’d had fractures but were not being treated for osteoporosis.
They first examined the bones’ microstructure and identified areas of osteoclast activity (“perforations”) versus microscopic fractures (“microcracks”). Then they subjected each sample to load-controlled tensile testing to determine how much strain the bone could withstand.
The results were revealing. The first group (no fractures) had the least amount of either perforations or microcracks. Both the second (untreated with fractures) and third (bisphosphonate-treated with fractures) groups had roughly equivalent amounts of perforations and microcracks. But the big difference was the volume of perforations versus microcracks: the untreated group had a significantly higher volume of perforations while the bisphosphonate group showed a significantly higher volume of microcracks.
Bisphosphonates and bone fracture risk
I’ve always maintained that the greatest issue when it comes to bone health isn’t thin bones — it’s weak ones. In healthy bone, microfractures stimulate bone turnover, which ultimately renews bone and makes it stronger — unless the activity of bone-building osteoblasts is outstripped by bone-removing osteoclasts.
It’s pretty clear that the untreated patients who’d had fractures were undergoing high bone turnover — that’s why they had more (and larger) osteoclastic perforations. But the bisphosphonates-treated group had significantly larger microcracks — which suggests that in the bisphosphonate group, either the bone is much less resilient and more prone to cracking under strain than normal bone, or the usual repair mechanisms aren’t working up to standard. Or both at the same time!
More to the point, it suggests that people treated with bisphosphonates have bones that are significantly weaker and more prone to fracture than either healthy people or people with high bone turnover.
The tensile strength testing performed on all three groups’ samples confirmed this: Where the normal group had a tensile strength (measured in megapascals) of 1.62 MPa, the untreated fracture group’s tensile strength was decreased by about 47% (to 0.86 MPa) — and the bisphosphonate group’s tensile strength was an astonishing 64% (0.58 MPa) below the normal group’s level.
This means that people treated with bisphosphonates have much weaker bones than even people at high risk of fracture due to high bone turnover!
So if using bisphosphonates leaves patients with slightly denser but significantly weaker bones, increasing the likelihood of a catastrophic fracture (never mind the other side effects), this leaves us asking, “What exactly is their benefit?
Ma S, Goh EL, Jin A, et al. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties. Sci Rep 2017;7:43399; DOI: 10.1038/srep43399.