Osteoporosis of the Spine: Drug Therapy

Therapeutic target

  • Avoidance of complications and further progression of bone destruction.

Therapy recommendations

Therapy scheme (applicable to DXA values only).

Age in years T-score (applicable to Dexa values only. The efficacy of pharmacotherapy has not been proven with certainty for peripheral fractures (broken bones) with a T-score > -2.0)
Ms Man -2,0 – -2,5 -2,5 – -3,0 -3,0 – -3,5 -3,5 – -4,0 < -4,0
50-60 60-70 No No No No Yes
60-65 70-75 No No No Yes Yes
65-70 75-80 No No Yes Yes Yes
70-75 80-85 No Yes Yes Yes Yes
> 70 > 85 Yes Yes Yes Yes Yes

In the case of a spontaneous vertebral body fracture, therapy is always indicated, regardless of the above therapeutic regimen.legend

  • Yes: therapy indicated
  • No: No therapy indicated

Raise therapy limit by +1.0 at:

  • Diabetes mellitus type 1
  • ≥ 3 low-traumatic fractures (broken bones) in the past 10 years as a single case decision (excl. finger, toe, skull, and ankle fractures)
  • Glucocorticoids, orally ≥ 2.5 mg and <7.5 mg prednisolone equivalent daily (exception: rheumatoid arthritis, here +0.5)

Raising the therapy limit by +0.5 at:

* If risk currently existing or terminated less than 12-24 months.

Start osteoporosis therapy according to the above therapeutic regimen (in bold drugs particularly suitable for reducing vertebral fracture risk):

  • Basic therapy (vitamin D: 800-1,000 I.U., calcium: 1,000 mg).
  • Postmenopausal osteoporosis:
    • Antiresorptive agents (bone resorption ↓):
    • Stimulants/osteoanabolic therapy (bone formation ↑).
      • Parathyroid hormone analog: Teriparatide; second-line agent for severe osteoporosis; Risk of vertebral fractures and nonvertebral fractures ↓In the VERO (VERtebral Fracture Treatment Comparisons in Osteoporotic Women) trial, there was a significantly greater reduction in the rate of vertebral fractures (vertebral fractures) in postmenopausal women with advanced osteoporosis and fragility fracture, when they received teriparatide (20 μg sc/d) instead of risedronate (35 mg/wk) in addition to baseline calcium and vitamin D therapy (24 months later, the rate of new vertebral fractures was 5.4 versus 12.0 percent (p < 0.001); clinical fractures occurred in only 4.8 versus 9.8 percent (p<0.0009).
    • Estrogen or estrogen/progestin therapy (hormone replacement therapy) in postmenopausal women <60 years of age and at high risk of fracture (first-line option for prevention and treatment of osteoporosis).
  • Special forms of osteoporosis in women (premenopausal osteoporosis; pregnancy-associated osteoporosis; senile osteoporosis (type II): see below.
  • Glucocorticoid-induced osteoporosis:
  • Osteoporosis in men:
    • Bisphosphonates: alendronate, risedronate, zoledronic acid (synonym: zoledronate); inhibit osteoclasts)/first-line agents.
    • Monoclonal antibodies: denosumab (IgG2 anti-RANKL antibody); also used for osteoporosis associated with hormone ablation (androgen deprivation therapy: ADT; hormone therapy that withholds the male sex hormone testosterone) in men with prostate cancer at increased risk of fracture (risk of bone fracture)
    • Parathyroid hormone analogue: teriparatide
  • Note: Clinical controls should initially be performed every 3 to 6 months after initiation of specific therapy.
  • See also under “Further Therapy.”
  • Fracture pain:
    • Analgesia according to WHO staging scheme:
      • Non-opioid analgesic (paracetamol, first-line agent).
      • Low-potency opioid analgesic (e.g., tramadol) + non-opioid analgesic.
      • High-potency opioid analgesic (eg, morphine) + non-opioid analgesic.
  • See also under “Further therapy”.

Further notes

  • In clinical trials in patients with advanced cancers, occurrence of increased incidence of new primary malignancies with denosumab compared with zoledronic acid.

Active ingredients (main indication) of basic therapy

Active ingredient group Active ingredient Dosage Special features
Calcium Calcium 1,000 mg/d
Vitamin D preparation Cholecalciferol( = vitamin D3) 800- 1,000 I.U./d For high risk of falls and/or fractures and low sunlight exposureOther indications: Rickets, osteomalacia

Postmenopausal osteoporosis

Active ingredients (main indication).

Bisphosphonates

Active ingredients Special features
Alendronate First-line agentAlso approved for women treated with glucocorticoidsKI in severe renal insufficiency.
Etidronate Second choice agent
Ibandronate Women with a T score < -3.0 at the femoral neckKI in severe renal insufficiency.
Risedronate Also approved for women treated with glucocorticoidsKI for severe renal insufficiency.
Zoledronic acid (synonym: zoledronate). Also approved for women who have been treated with glucocorticoids

Note: Should be given after proximal femur fracture no earlier than two weeks postoperatively.KI in severe hepatic/renal insufficiency

  • Mode of action: inhibit osteoclasts (bone-degrading cells), leading to an increase in bone mass
  • Indications: postmenopausal osteoporosis and glucocorticoid-induced osteoporosis.
  • Contraindications: including hypocalcemia (calcium deficiency).
  • Alendronate, risedronate, zoledronic acid (synonym: zoledronate) has been shown to have an effect on both vertebral and non-vertebral and hip fractures (due toFragility fractures).
  • Dosage instructions: 30 minutes before breakfast with plenty of water followed by the need to sit upright.
  • The U.S. Food and Drug Administration (FDA) recommends discontinuation of bisphosphate therapy after 5 years (“drug holiday”); this excludes patients who continue to be classified in the high-risk group

Selective estrogen receptor modulator (SERM).

Mode of action Special features
Bazedoxifene KI in hepatic/severe renal insufficiencyKI unexplained uterine bleeding and signs or symptoms of endometrial cancer.
Raloxifene
  • Mode of action: inhibits bone resorption
  • Indications: postmenopausal osteoporosis
    • Bazedoxifene: Reduction of vertebral fractures: + (A); reduction of nonvertebral fractures: + (B) (fracture-reducing for selected patients (subgroups)).
    • Raloxifene: Reduction of vertebral fractures: + (A); reduction of nonvertebral fractures: -.
  • Potential risk reduction for the occurrence of estrogen receptor-positive breast carcinomas.
  • Significant fracture reduction has been demonstrated for raloxifene and bazedoxifene over eight and seven years, respectively.
  • Caveat: increased risk of thrombosis and increased incidence of fatal stroke.

Monoclonal antibodies

Drug group Active ingredients Special features
gG2 anti-RANKL antibody Denosumab No dose adjustment for renal insufficiency (renal impairment)
Sclerostin antibody Romosozumab Adequate intake of calcium and vitamin D before and during treatment
  • Mode of action of denosumab: monoclonal antibody that mimics the effects of osteoprotegerin (OPG) in bone metabolism; IgG2 anti-RANKL antibody that binds with very high affinity to RANKL, inhibiting its interaction with RANK.
  • Denosumab has been shown to have an effect on both vertebral, non-vertebral, and hip fractures (due tofragility fractures)
  • Contraindications: including hypocalcemia (calcium deficiency).
  • Cave: osteonecrosis of the jaw bone and external auditory canal under therapy with bisphosphonates and denosumab.
  • Multiple vertebral body fractures after discontinuation of denosumab.
  • In clinical trials in patients with advanced cancers, occurrence of increased incidence of new primary malignancies with denosumab compared with zoledronic acid.
  • Mode of action of romosozumab: sclerostin antibody that inhibits osteoblast (bone-forming cell) function, differentiation, proliferation, and survival (promotes bone formation and, to a lesser extent, additionally inhibits bone resorption).
  • Indication of Romosozumab: treatment of manifest osteoporosis in postmenopausal women with significantly increased risk of fracture (risk of bone fracture.
  • Contraindications: hypocalcemia (calcium deficiency); history of myocardial infarction (heart attack) or apoplexy (stroke).
  • Side effects: Headache, joint pain, and injection site pain.

Parathyroid hormone analogue

Active ingredients Special features
Teriparatide KI in severe renal insufficiency
  • Mode of action: bone-building (anabolic) properties through a direct stimulation of osteoblasts; also increases the absorption of calcium and promotes calcium reabsorption by the kidneys
  • Dosage instructions: Application maximum 24 months!

Hormones

Active substances Dosage Special features
Estrogen(progestin) Various Second choice means
  • Mode of action: antiresorptive
  • Side effects: cardiovascular, risk of mammary carcinoma (breast cancer).

Prophylaxis and therapy for special forms of osteoporosis in women

Premenopausal osteoporosis

The cause of osteoporosis (bone loss) in premenopausal women is the result of too low maximum bone density (“peak bone mass“) and/or increased bone loss. Drug therapy should only be considered in cases of significantly decreased bone density (DXA values) and presence of severe risk factors. In the presence of hypogonadism, hormone replacement therapy (HRT) is the optimal therapy. Bisphosphate therapy is only considered if there is an inadequate response to HRT. Raloxifene may also be an alternative therapy.

Pregnancy-associated osteoporosis

During the lactation period, a woman secretes approximately 500 mg of calcium daily into breast milk. During pregnancy or postpartum, fractures are the result of previous calcium and vitamin D deficiencies and are not a consequence of pregnancy!If fractures occur during pregnancy, the patient should wean as early as possible so that there are no further calcium deficiencies on the part of the maternal skeleton. Bisphosphate therapy (“off-label use“) may be considered.

Senile osteoporosis (type II)

This type of osteoporosis – also called senile osteoporosis – equally affects women and men older than 70 years. In this form of osteoporosis, the compacta is increasingly affected in addition to the cancellous bone. This is why fractures of the long bones predominate. In this disease, also known as senile osteoporosis, vitamin D resistance and vitamin D deficiency occur in old age, which leads, among other things, to a reduction in calcium resorption from the intestine. Therapy with at least 1,000-2,000 IU vitamin D3 and 1,000 mg calcium daily. Furthermore, antiresorptive therapy with bisphosphates (first choice) if necessary also osteoanabolic therapy with a parathyroid hormone analogue.

Glucocorticoid-induced osteoporosis

Agents (main indication).

Active ingredient group Active ingredients Special features
Calcium Calcium Prophylaxis
Vitamin D preparation Cholecalciferol( = vitamin D3) ProphylaxisOther indications: Rickets, osteomalacia
Bisphosphonates Alendronate Male + femaleKI in severe renal insufficiency.
Risedronate MsKI in severe renal insufficiency.
Zoledronic acid (synonym: zoledronate) Male + femaleKI in severe hepatic/renal insufficiency.
  • Mechanism of action: Bisphosphonates inhibit osteoclasts, leading to an increase in bone mass
  • Indications:
    • DXA-T value < -1.5 and
    • Systemic glucocorticoid therapy > 3 months or
    • Osteoporotic fracture
  • Alendronate, risedronate, zoledronate have been shown to have an effect on both vertebral and non-vertebral and hip fractures (due tofragility fractures)
  • Dosage instructions: 30 minutes before breakfast with plenty of water followed by the need to sit upright.

Monoclonal antibodies

Drug group Active ingredients Special features
gG2 anti-RANKL antibody Denosumab No dose adjustment for renal insufficiency
  • Mode of action: monoclonal antibody that mimics the effects of osteoprotegerin (OPG) in bone metabolism; IgG2 anti-RANKL antibody that binds with very high affinity to RANKL, inhibiting its interaction with RANK.
  • Denosumab has been shown to have an effect on both vertebral, non-vertebral, and hip fractures (due tofragility fractures)
  • In a phase III study, denosumab was superior to bisphosphonate risedronate.
  • Cave: osteonecrosis of the jawbone and external auditory canal during therapy with bisphosphonates and denosumab.
  • Multiple vertebral body fractures after discontinuation of denosumab.

Parathyroid hormone analogue

Active ingredients Special features
Teriparatide KI in severe renal insufficiency
  • Mode of action: bone-building (anabolic) properties through a direct stimulation of osteoblasts; also increases the absorption of calcium and promotes calcium reabsorption by the kidneys
  • Dosage information: Application maximum 24 months

Osteoporosis in men

Therapy recommendations

For men with decreased bone mineral density and increased fracture risk, the antibody denosumab is an approved treatment option. Bisphosphonates

Active ingredients Special features
Alendronate Also used in men >60th lyoFirst-lineKI in severe renal insufficiency.
Risedronate KI in severe renal insufficiency
Zoledronic acid (synonym: zoledronate). KI in severe hepatic/renal insufficiency.
  • Mode of action: inhibit osteoclasts, leading to an increase in bone mass
  • Indications: postmenopausal osteoporosis and glucocorticoid-induced osteoporosis.
  • Dosage instructions: 30 minutes before breakfast with plenty of water followed by the need to sit upright.
  • Note: Jaw necrosis can be largely avoided by regular dental checkups, improved oral hygiene, plastic wound closure and tooth extraction under antibiotic prophylaxis.

Monoclonal antibodies

Drug group Active ingredients Special features
gG2 anti-RANKL antibody Denosumab No dose adjustment for renal insufficiency
  • Mode of action: monoclonal antibody that mimics the effects of osteoprotegerin (OPG) in bone metabolism; IgG2 anti-RANKL antibody that binds with very high affinity to RANKL, inhibiting its interaction with RANK.
  • Indications:
    • Osteoporosis associated with hormone ablation in men with prostate carcinoma at increased risk of fracture.
    • S3 guideline: first-line therapy for all skeletal sites [recommendation grade A].

Parathyroid hormone analogue

Active ingredients Special features
Teriparatide KI in severe renal insufficiency
  • Mode of action: bone-building (anabolic) properties through a direct stimulation of osteoblasts; also increases the absorption of calcium and promotes calcium reabsorption by the kidneys
  • Dosage information: Application maximum 24 months
  • Contraindications: Paget’s disease, malignant bone tumors, bone metastases; other restrictions: Hypercalcemia, radiotherapy of the skeleton, elevated alkaline phosphatase, renal insufficiency.

Fracture pain

Therapy goal for fracture pain.

Drug therapy for vertebral fracture is intended to relieve pain, allowing mobilization as soon as possible to avoid sequelae.

Active ingredients (main indications)

Analgesics

Drug group Active ingredient Special features
Non-acidic analgesics Paracetamol Dose adjustment in renal/liver insufficiency.
Paracetamol +codeine phosphate Dose adjustment in renal/liver insufficiency.
NSAIDS Acetylsalicylic acid Dose adjustment in renal/hepatic insufficiencyGastrointestinal NW
Ibuprofen Dose adjustment for renal/hepatic insufficiencyGastrointestinal NW
Opioids Morphine (high potency) Dose adjustment for renal/hepatic insufficiencyShort-term only for very severe, uncontrollable pain.
Tramadol (low potency) Dose adjustment for renal/hepatic insufficiency during long-term therapy
  • Mode of action of nonacidic analgesics: reversible cyclooxygenase inhibition → analgesic, antipyretic; metamizole weakly antiphlogistic.
  • Mode of action Ibuprofen: inhibition of cyclooxygenase.
  • Mode of action opioid analgesics: bind to opioid receptors → μ-, κ-, δ-receptors.
  • Indications: Short-term use for severe pain

All agents should be used for as short a time as possible because of side effects and interactions in patients who are often multimorbid.

Osteoporosis and long-term anticoagulation

Comparing for a nonvitamin K-dependent oral anticoagulant (NOAK) or a vitamin K antagonist (VKA), a first retrospective analysis demonstrated a low risk for any fractures in both groups; however, there was a significant difference in favor of anticoagulation with NOAKs (3.09% vs 3.77%; adjusted HR 0.85, 95% CI 0.74-0.97). This was also true for osteoporotic fractures, where NOAKs were associated with a relatively 15% lower risk (2.29% vs 2.82%; adjusted HR 0.85, 95% CI 0.72-0.99).

Supplements (dietary supplements; vital substances)

Appropriate dietary supplements should contain the following vital substances: